Next Article in Journal
Effect of Annealing on the Structure of Composite Passivation Films Prepared by Magnetron Sputtering Deposition on the Surface of HgCdTe
Next Article in Special Issue
Assessment of Physicochemical, Anticancer, Antimicrobial, and Biofilm Activities of N-Doped Graphene
Previous Article in Journal
Improvement of Mechanical Properties and Microstructure of Cementitious Materials in a Hot-Dry Environment
Previous Article in Special Issue
Nano- and Crystal Engineering Approaches in the Development of Therapeutic Agents for Neoplastic Diseases
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Crystals
Volume 12
Issue 7
10.3390/cryst12070982
crystals-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

The Crystal Structure of 3-Amino-1-(4-Chlorophenyl)-9-Methoxy-1H-Benzo[f]Chromene-2-Carbonitrile: Antimicrobial Activity and Docking Studies

by
Rawda M. Okasha
1,
Ahmed M. Fouda
2,
Majed A. Bajaber
2,
Hazem A. Ghabbour
3,
Abd El-Galil E. Amr
4,5,*,
Ahmed M. Naglah
4,6,
Abdulrahman A. Almehizia
4,
Ahmed A. Elhenawy
7,8,* and
Ahmed M. El-Agrody
7,*
1
Chemistry Department, Faculty of Science, Taibah University, Medina 30002, Saudi Arabia
2
Chemistry Department, Faculty of Science, King Khalid University, Abha 61413, Saudi Arabia
3
Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt
4
Drug Exploration and Development Chair (DEDC), Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
5
Applied Organic Chemistry Department, National Research Centre, Dokki, Giza 12622, Egypt
6
Peptide Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt
7
Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt
8
Chemistry Department, Faculty of Science and Art, AlBaha University, Mukhwah, Al Bahah 65731, Saudi Arabia
*
Authors to whom correspondence should be addressed.
Crystals 2022, 12(7), 982; https://doi.org/10.3390/cryst12070982
Submission received: 31 May 2022 / Revised: 22 June 2022 / Accepted: 8 July 2022 / Published: 14 July 2022
(This article belongs to the Special Issue Novel Nanomaterials for Catalytic and Biological Applications)
Browse Figures
Versions Notes

Abstract

:
Compound 3-amino-1-(4-chlorophenyl)-9-methoxy-1H-benzo[f]chromene-2-carbonitrile (4), was synthesized via the reaction of 7-methoxynaphthalen-2-ol (1), 4-chlorobenzaldehyde (2), and malononitrile (3) in an ethanolic piperidine solution under microwave irradiation. The synthesized pyran derivative 4 was asserted through spectral data and X-ray diffraction. The molecular structure of compound 4 was established unambiguously through the single crystal X-ray measurements and crystallized in the Triclinic, P-1, a = 8.7171 (4) Å, b = 10.9509 (5) Å, c = 19.5853 (9) Å, α = 78.249 (2)°, β = 89.000 (2)°, γ = 70.054 (2)°, V = 1717.88 (14) Å3, Z = 4. The target molecule has been screened for antibacterial and antifungal functionality. Compound 4 exhibited favorable antimicrobial activities that resembled the reference antimicrobial agents with an IZ range of 16–26 mm. In addition, MIC, MBC, and MFC were assessed and screened for molecule 4, revealing bactericidal and fungicidal effects. Lastly, a molecular docking analysis was addressed and conducted for this desired molecule.

1. Introduction

The crystalline configurations of drug candidates have amassed substantial appreciation as a critical criterion for rational drug design with the manipulation of their functional moieties impacting the drug’s structure–activity relationship. Generally, the attained crystallographic data offer explicit/precise structural identification and absolute configuration [1,2,3,4,5,6], which accordingly elucidates the performance of the novel drugs without triggering the adverse response of the biological system stimuli. Of the drug candidates with an elevated disposition to forge crystallographic structures, chromene compounds are among the most notorious and prosperous [7,8,9]. The comprehensive biomedical features of chromene molecules have motivated scientific figures within the drug discovery biosphere to cultivate new derivatives of this class of materials and explore their novel biological characteristics. Chromenes have been renowned for their incredible biological functions, which assisted their assimilation into various applications such as antimicrobial activities [10,11,12,13,14], hypolipidemic [15], antileishmanial, antiviral, anti-HIV, antianaphylactic activities [16,17,18], insecticidal [19], targeting of c-Src kinase enzyme [20,21], anticancer and cytotoxic activities [22,23,24,25], cell cycle analysis, apoptotic effects, caspase 3/7, and inhibition of the topoisomerase enzyme [26,27,28,29,30,31,32,33]. Among the synthetic strategies to acquire chromene molecules, microwave irradiation is one of the most efficacious and eco-friendly procedures, which facilitates the isolation of the desired compounds in a short period of time and results in good yields [34,35,36,37]. Furthermore, the dihydrofolate reductase (DHFR) enzyme used as a therapeutic target in the treatment of infections through NADPH is used in the reduction of DHFR and is involved in the synthesis of cell proliferation raw material [38]. DHFR inhibitors are widely used in the treatment of fungal, bacterial, and mycobacterial infections through block DNA replication as well as in fighting cancer [39]. In addition, the chromene derivatives are used as potential agents against DHFR [40].
In continuation of our efforts to discover oxygen-heterocyclic derivatives with promising antimicrobial and antitumor activities [41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57], we present the synthesis of 3-amino-1-(4-chlorophenyl)-9-methoxy-1H-benzo[f]chromene-2-carbonitrile and portray its crystallographic structure. Moreover, the antimicrobial behavior of the target molecule is evaluated and its minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentrations (MFC) are appraised. Additionally, a molecular docking assessment of the novel compound is addressed and granted.

2. Results and Discussion

2.1. Chemistry

The route adopted for the preparation of compound 4 is depicted in Scheme 1. The synthesis was initiated by reacting 7-methoxynaphthalen-2-ol (1) with 4-chlorobenzal- dehyde (2) and malononitrile (3) in an ethanolic–piperidine solution under microwave irradiation conditions to furnish 3-amino-1-(4-chlorophenyl)-9-methoxy-1H-benzo[f]-chromene-2-carbonitrile (4). By repeating the reaction at various watt powers (200, 300, 400 W) and time intervals (1, 1.5, 2 min.), the best results were obtained by employing 400 W with a 2 min. reaction period, which delivered the maximum yield for compound 4. TLC was employed to monitor the reaction.

2.2. Optical Activity

Compound 4 has a chiral feature; consequently, this specific rotation was gauged, utilizing a Carl Zeiss polarimeter to attribute the stereochemistry of the 1-position to the 1H-benzo[f]-chromene moiety. Results revealed that compound 4 has zero rotation (meaning the molecule is optically inactive) and is obtained in the form of a racemic (±) mixture [26,27,28], as illustrated in Scheme 1.

2.3. Spectroscopic Data

The structure and purity of compound 4 were substantiated through spectral analyses, including: IR, 1H NMR, 13C NMR, MS, and X-ray single crystal (see Supplementary Materials, Figures S1–S3).

2.4. Crystal Data

In the title compound 4, C21H15ClN2O2, the crystallographic data and purification information are outlined in Table 1. The asymmetric unit of molecule 4 incorporates two independent compounds, which is witnessed in Figure 1. All the bond lengths and angles are in normal ranges [58]. As displayed in the crystal packing (Figure 2), the molecular components of compound 4 were linked through two intermolecular hydrogen bonds and two intramolecular hydrogen bonds, as shown in Table 2.

2.5. Biological Activity

2.5.1. Antimicrobial Activity Assay

Molecule 4 was estimated through a preliminary screening of its antibacterial activity via the agar diffusion methodology, employing a Mueller–Hinton agar medium for bacteria and a Sabouraud’s agar medium for fungi [59]. The analyzed collections encompassed three Gram-positive species of pathogenic bacteria: Staphylococcus aureus (RCMB 000106), Bacillus subtilis (RCMB 000108), and Staphylococcus epidermtitis (RCMB 000107); three Gram-negative bacteria: Enterococcus cloaca (RCMB 000101), Escherichia coli (RCMB 000103), and Salmonella typhimurium (RCMB 000103), utilizing reference antibiotic drugs Ampicillin and Gentamycin (5 μg/mL). Compound 4 was also scrutinized against three fungi: Aspergillus fumigatus (RCMB 002003), Aspergillus flavus (002002), and Candida albicans (RCMB 005003), utilizing the reference antibiotic Ketoconazole (5 μg/mL). The minim zone of inhibition (IZ) in mm ± standard deviation beyond the well diameter (6 mm) was established, employing a 5 μg/mL concentration of compound 4. Dimethyl sulfoxide (DMSO) was utilized as a blank and exhibited no antimicrobial activity. The inhibitory impacts of the synthetic compound in evaluation against these organisms are illustrated in Table 3. Compound 4 showed lower IZ than reference drugs against most of the tested microorganisms (S. aureus, S. epid, E. cloaca, S. typhi and A. fumigates). Furthermore, its compound displayed the same IZ with reference inhibitors against B. subtili and A. flavus.

2.5.2. MIC, MBC/MFC Studies

MIC denotes the minimum inhibitory concentration (the lowest concentration required to inhibit bacterial growth), MBC to the mean bactericidal concentration (the lowest concentration of the synthesized drugs required to kill specific bacteria), and MFC to the minimum fungicidal concentration (the lowest concentration of the synthesized drugs required to kill specific fungi). MIC, MBC, and MFC were assayed for the active compound 4 in μg/mL. The examined antimicrobial data (MICs/MBCs and MICs/MFCs) of the desired molecule 4 and their standardized drugs are supplied in Table 4.
Antimicrobials are regularly perceived as bactericidal/fungicidal if the MBC/MFC quantities do not exceed four times the MIC [60]. Molecule 4 has 2 × MIC = MBC value in the instance of S. aureus, B. subtilis, E. cloaca, and S. typhimurium bacteria. Furthermore, molecule 4 possesses 2 × MIC = MFC value in the instance of A. fumigatus and A. flavus fungi. Results in Table 3 and Table 4 indicated that molecule 4 demonstrated much stronger antibacterial behavior against S. aureus, B. subtilis, S. epidermtitis, E. cloaca, E. coli, and S. typhimurium with an inhibition zone (Figure S4, Supplementary Material) ranging from 16–26 mm and MIC & MBC of 6.25–50 μg/mL compared to the quantities of the reference drug Ampicillin (IZ = 24–28 mm and MIC/MBC = 6.25 μg/mL) and Gentamycin (IZ = 17–30 mm and MIC/MBC = 6.25–50 μg/mL). Moreover, compound 4 (IZ = 15 and 16 mm) yielded a much stronger antifungal activity against A. fumigatus and A. flavus with MIC/MFC of 6.25 and 12.5 μg/mL in appraisal against Ketoconazole (IZ = 17 and 16 mm).

2.5.3. Structure-Activity Relationship (SAR) Study

The antimicrobial activity of molecule 4 is depicted in Table 3. The SAR study revealed that compound 4 with inhibitory effects ranging from 22–26 and 16–31 mm illustrated stronger vitality against the Gram-positive tested bacteria (S. aureus, B. subtilis, S. epidermtitis), Gram-negative tested bacteria (E. cloaca, E. coli, S. typhimurium), and inhibitory effects ranging from 15–21 mm against the tested fungi (A. fumigates, A. flavus, C. Albicans) in evaluation of the standard antibiotics Ampicillin (IZ = 24–28 mm), Gentamycin (IZ = 17–30 mm), and Ketoconazole (IZ = 16–20 mm), respectively. The presence of a hydrophobic electron-withdrawing substituent (the chlorine atom at the para-position on the phenyl group at the 1-position) alongside an electron-donating substituent (the methoxy group at the 9-position of the 1H-benzo[f]chromene moiety) has enhanced the antimicrobial behavior significantly.

2.6. Molecular Docking Analysis

According to the inhibitory functionalities of molecule 4, the molecular docking was performed against dihydrofolate reductase “DHFR”, and its positioning of the active compound within the substrate binding pocket assists in the comprehension of its mode of interaction. We selected two crystal structures for the hDHFR protein ((PDB): 4DFR [61]) and (PDB ID: 3NTZ [62]). Compound 4, the reference inhibitor Methotrexate, and reference drugs (Ampciline, Gentamicin, Ketocwere) were stationed in the binding pocket of enzyme s, and its binding interactions were illustrated in Figure 3 and Figure 4.
The mGenTHERADER generated the 3D loop structure of DHFR and the applied docking framework. The biological behavior was represented as binding-interaction BI term for 3-amino-1-(4-chlorophenyl)-9-methoxy-1H-benzo[f]Chromene-2-carbonitrile over DHFR, then compared with Methotrexate and reference drugs. Compound 4 re-docked and showed promising (root mean square deviation, RMSD = 0.93, 0.52 Å) compared to other compounds against both enzymes. The reference inhibitor reported interaction with vital binding site of 4DFR (ASP27, ILE5, ILE94, ARG52, ARG57). Compound 4 showed BI = −7.69 Kcal/mol. compared to Methotrexate BI = −8.86 Kcal/mol (Table 5). BI was arranged as 4 > Gentamicin > Methotrexate > Ketoconazole > Ampicillin. Compound 4 formed a strong H-bond between methoxy and vital ASP27 with a distance 1.2° and E = −1.69(kcal/mol), compared to Methotrexate, which showed an H-bond with ASP27 and formed a distance of 2.88° and ΔE = −5.4 (kcal/mol. The interaction mode for compound 4 and reference drugs in the binding pocket had the same manner as the reference inhibitor and might be responsible for the high inhibitory activity for compound 4.
In case of 3NTZ; Compound 4 showed the highest BI = −9.43 Kcal/mol. compared to other inhibitors (Table 5). BI was arranged for other inhibitors as Gentamicin > Ketoconazole > Ampciline > Methotrexate. The active site of 3NTZ comprises the following amino acid residues: Val 6, Ala 9, Leu 22, Pro 25, Asp 27, Leu 28, Glu30, Gln35, Phe 31, Ser 49, Ile 50, Thr56, Leu62, and Thr 111. Compound 4 formed a strong H-bond between the amino group and Ala9 and formed a π-π bond between Leu22. Methotrexate showed an H-bond with Glu30 and Arg70 (Figure 4). Therefore, the interaction with vital amino acids of hDHFR plays an important role in the inhibitory effects of this compound. Furthermore, the activities of compound 4 were due to the presence of the amino and cyano groups.

3. Experimental Section

3.1. Materials and Equipment’s

All chemicals purchased and instruments used are mentioned in the Supplementary Material.

3.2. Synthesis of 3-Amino-1-(4-Chlorophenyl)-9-Methoxy-1H-Benzo[f]Chromene-2-Carbonitrile (4)

Yellow needles, yield 89%, m.p. 257–258 °C (Literature procedure: ionic liquids condition, yield 79%; m.p. 257–259 °C [63] microwave condition, yield 89%; m.p. 257–258 °C [64]).

3.3. Biological Screening

Compound 4 was screened for its in vitro antimicrobial activities against Gram-positive species of pathogenic bacteria: Staphylococcus aureus, Bacillus subtilis, and Staphylococcus epidermtitis; three Gram-negative bacteria Enterococcus cloaca, Escherichia coli, and Salmonella typhimurium using the standard antibiotics Ampicillin and Gentamycin as reference drugs. The investigation also included three fungi: Aspergillus fumigatus, Aspergillus flavus, and Candida albicans using the standard antibiotic, Ketoconazole, as a reference drug [59]. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentrations (MFC) were determined as previously reported [60]. The antimicrobial activities were performed at the Regional Centre for Mycology & Biotechnology (RCMP), Al-Azhar University.

3.4. X-ray Crystallography Analysis

Compound 4 was obtained as single crystals by slow evaporation from an ethanol solution of the pure compound at room temperature with CCDC 2054799. Data were collected on a Bruker APEX-II D8 Venture area diffractometer, equipped with graphite monochromatic Mo Kα and Cu Kα radiations at 293 (2) K. Cell refinement and data reduction were carried out by Bruker SAINT. SHELXTL-2018/3 [65,66] was used to solve the structure.

3.5. Docking Assay

Small ligands (4 and methotrexate) were prepared using the DFT theory with the Becke3-Lee-Yang-parr (B3LYP) level using 6-311G ** basis as implemented in Gaussian 09W [67]. The optimization geometry for molecular structures was carried out and used in the docking experiment.
The 3D crystal-structure for the GHFR model was prepared using the glide-tool as described [68,69].

4. Conclusions

In an effort to develop potent antimicrobial agents, compound 4 was synthesized and characterized employing an X-ray diffraction technique. Subsequently, the antimicrobial behavior of molecule 4 was appraised against different pathogenic bacterial and fungal strains, which demonstrated promising antimicrobial activities in correspondence with the reference antimicrobial agents exhibiting an IZ range of 16–31 mm. Furthermore, the values of MIC, MBC, and MFC were ascertained for compound 4, disclosing its bactericidal and fungicidal activites. The molecular docking analysis was performed to relate our biological findings with the chemical structure and to show their ability to bind with the DHFR active site similar to Methotrexate.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/cryst12070982/s1, Figure S1: 1H NMR of compound 4; Figure S2: 1H NMR 8–6 ppm of compound 4; Figure S3: 13 C NMR of compound 4, and Compound 4_checkCIF; Figure S4: The inhibition zone of compound 4.

Author Contributions

A.M.E.-A., A.M.F., A.E.-G.E.A., A.M.N., R.M.O. and A.A.A. designed the proposed methods and analyzed the spectral data; A.M.E.-A. performed the experiment and implemented the biological study; A.A.E. performed DFT theoretical calculations; M.A.B. analyzed the biological data and reviewed and R.M.O. edited the draft. H.A.G. carried out and wrote the X-ray processes. All authors have read and agreed to the published version of the manuscript.

Funding

This work was funded by the Deanship of Scientific Research, King Saud University, through vice Deanship of Scientific Research Chairs.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data is available in this article and Supplementary Materials.

Acknowledgments

The authors extend their appreciation to the Deanship of Scientific Research, King Saud University for funding through Vice Deanship of Scientific Research Chairs; (Drug Exploration and Development Chair).

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Amr, A.-G.E.; El-Mawgoud, H.K.A.; El-Agrody, A.M.; Al-Omar, M.A.; Alsultan, M.S. X-ray, Microwave Assisted Synthesis and Spectral Data of 3-Amino-1-(3,5-dibromo-2-methoxyphenyl)-8-methoxy-1H-benzo[f]chromene-2-carbonitrile. J. Comput. Theor. Nanosci. 2017, 14, 3930–3935. [Google Scholar] [CrossRef]
  2. Mohamed, H.M.; Amr, A.-G.E.; El-Agrody, A.M.; Al-Omar, M.A.; Ghabbour, H.A. Crystal structure of 3-amino-1-(4-bromophenyl)-9-methoxy-1H-benzo[f]chromene-2-carbonitrile, C21H15BrN2O2. Z. Krist. New Cryst. Struct. 2017, 232, 561–563. [Google Scholar] [CrossRef] [Green Version]
  3. El-Agrody, A.M.; Al-Omar, M.A.; Amr, A.-G.E.; Ng, S.W.; Tiekink, E.R.T. 3-Amino-1-(4-fluorophenyl)-8-methoxy-1H-benzo[f]chromene-2-carbonitrile. Acta Crystallogr. Sect. E Struct. Rep. Online 2013, 69, o476–o477. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  4. Amr, A.-G.E.; El-Agrody, A.M.; Al-Omar, M.A.; Ng, S.W.; Tiekink, E.R.T. 3-Amino-1-(4-fluorophenyl)-7-methoxy- 1H-benzo [f]chromene-2-carbonitrile. Acta Crystallogr. Sect. E Struct. Rep. Online 2013, 69, o478–o479. [Google Scholar] [CrossRef] [Green Version]
  5. Al-Dies, A.-A.M.; Amr, A.-G.E.; El-Agrody, A.M.; Chia, T.S.; Fun, H.-K. 2-Amino-4-(4-fluorophenyl)-6-methoxy-4H-benzo [h]chromene-3-carbonitrile. Acta Crystallogr. Sect. E Struct. Rep. Online 2012, 68, o1934–o1935. [Google Scholar] [CrossRef] [Green Version]
  6. Okasha, R.M.; Amr, A.E.G.E.; El-Agrody, A.M.; Al-Omar, M.A.; Ghabbour, H.A. Synthesis, X-ray characterization and antimicrobial activity of 3-amino-1-(2, 4-dichlorophenyl)-8-methoxy-1H-benzo [f] chromene-2-carbonitrile. J. Comput. Theor. Nanosci. 2017, 14, 5717–5721. [Google Scholar] [CrossRef]
  7. Radwan, H.A.M.; El-Mawgoud, H.K.A.; El-Mariah, F.; El-Agrody, A.M.; Amr, A.-G.E. Single-Crystal Structure and Antimicrobial Activity of Ethyl 3-Amino-1-(4-chlorophenyl)-9-hydroxy-1H-benzo[f]chromene-2-carboxylate Combined with Ethyl α-Cyano-4-chlorocinnamate. Russ. J. Gen. Chem. 2020, 90, 299–304. [Google Scholar] [CrossRef]
  8. El Gaafary, M.; Simmet, T.; Mohamed, H.M.; Elhenawy, A.A.; El-Agrody, A.A.-G.E.; Ghabbour, H.A.; Almehizia, A.A. Synthesis, Cytotoxic Activity, Crystal Structure, DFT Studies and Molecular Docking of 3-Amino-1-(2,5-dichloro-phenyl)-8-methoxy-1H-benzo[f]chromene-2-carbonitrile. Crystals 2021, 11, 184. [Google Scholar] [CrossRef]
  9. El-Agrody, A.M.; Fouda, A.M.; Mohamed, H.M.; Alshahrani, M.Y.; Ghabbour, H.A.; Amr, A.-G.E.; Okasha, R.M.; Almehizia, A.A.; Elhenawy, A.A. The Crystal Structure of2-Amino-4-(2,3-Dichlorophenyl)-6-Methoxy-4H-Benzo[h]-[h]chromene-3-Carbonitrile: Antitumor and Tyrosine Kinase Receptor Inhibition Mechanism Studies. Crystals 2022, 12, 737. [Google Scholar] [CrossRef]
  10. Fouda, A.M.; Hassan, A.H.; Eliwa, E.M.; Ahmed, H.E.A.; Al-Dies, A.A.M.; Omar, A.M.; Nassar, H.S.; Halawa, A.H.; Aljuhani, N.; El-Agrody, A.M. Targeted potent antimicrobial benzochromene-based analogues: Synthesis, computational studies, and inhibitory effect against 14a-Demethylase and DNA Gyrase. Bioorg. Chem. 2020, 105, 104387. [Google Scholar] [CrossRef]
  11. Abd El-Mawgoud, H.K.; Radwan, H.A.M.; El-Mariah, F.; El-Agrody, A.M. Synthesis, Characterization, Biological Activity of Novel 1H-benzo[f ]chromene and 12H-benzo[f ]chromeno[2,3-d]pyrimidine Derivatives. Lett. Drug Des. Discov. 2018, 15, 857–865. [Google Scholar] [CrossRef]
  12. Mohamed, H.M.; Abd EL-Wahab, A.H.F.; El-Agrody, A.M.; Bedair, A.H.; Eid, F.A.; Khafagy, M.M.; Abd-EL-Rehem, K.A. Synthesis and characterization of new diiodocoumarin derivatives with promising antimicrobial activities. Beilstein J. Org. Chem. 2011, 7, 1688–1696. [Google Scholar] [CrossRef]
  13. Okasha, R.M.; Albalawi, F.F.; Afifi, T.H.; Fouda, A.M.; Al-Dies, A.M.; El-Agrody, A.M. Structural Characterization and Antimicrobial Activities of 7H-Benzo[h]chromeno[2,3-d]pyrimidine and 14H-Benzo[h]chromeno[3,2-e] [1,2,4]-triazolo[1,5-c]pyrimidine Derivatives. Molecules 2016, 21, 1450. [Google Scholar] [CrossRef] [Green Version]
  14. Sabry, N.M.; Mohamed, H.M.; Khattab, E.S.A.E.H.; Motlaq, S.S.; El-Agrody, A.M. Synthesis of 4H-chromene, coumarin, 12H-chromeno[2,3-d]pyrimidine derivatives and some of their antimicrobial and cytotoxicity activities. Eur. J. Med. Chem. 2011, 46, 765–772. [Google Scholar] [CrossRef]
  15. Sashidhara, K.V.; Kumar, M.; Modukuri, R.K.; Srivastava, A.; Puri, A. Discovery and synthesis of novel substituted benzocoumarins as orally active lipid modulating agents. Bioorg. Med. Chem. Lett. 2011, 21, 6709–6713. [Google Scholar] [CrossRef]
  16. Foroumadi, A.; Emami, S.; Sorkhi, M.; Nakhjiri, M.; Nazarian, Z.; Heydar, S.; Ardestani, S.; Poorrajab, F.; Shafiee, A. Chromene-based synthetic chalcones as potent anti-leishmanial agents: Synthesis and biological activity. Chem. Biol. Drug Des. 2010, 75, 590–596. [Google Scholar] [CrossRef]
  17. Abbaspour-Gilandeh, E.; Azimi, S.C. Li(OHCH2CH2NH2)(CF3OAC): A novel and homogeneous acidic ionic liquid catalyst for efficient synthesis of 2-amino-4H-chromene derivatives. Iran. J. Catal. 2014, 4, 281–288. [Google Scholar]
  18. Denish, C.K.; Hetal, K.P.; Nilesh, K.G. Synthesis, characterization & anti-HIV activity of 4-Hydroxy-3-(5-methylisoxazol-3-yl)pyrano(3,2-c)chromene-2,5-dione. AJBPR 2012, 2, 126–130. [Google Scholar]
  19. Khurana, J.M.; Magoo, D.; Aggarwal, K.; Aggarwal, N.; Kumar, R.; Srivastava, C. Synthesis of novel 12-aryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-thiones and evaluation of their biocidal effects. Eur. J. Med. Chem. 2012, 58, 470–477. [Google Scholar] [CrossRef]
  20. Ahmed, H.E.A.; El-Nassag, M.A.A.; Hassan, A.; Okasha, R.M.; Ihmaid, S.; Fouda, A.M.; Afifi, T.H.; Aljuhani, A.; El-Agrody, A.M. Introducing novel potent anticancer agents of 1H-benzo[f]chromene scaffolds, targeting c-Src kinase enzyme with MDA-MB-231 cell line anti-invasion effect. J. Enzym. Inhib. Med. Chem. 2018, 33, 1074–1088. [Google Scholar] [CrossRef] [Green Version]
  21. Ahmed, H.E.A.; El-Nassag, M.A.A.; Hassan, A.H.; Mohamed, H.M.; Halawa, A.H.; Okasha, R.M.; Ihmaid, S.; Abd El-Gilil, S.M.; Khattab, E.S.A.E.H.; Fouda, A.M.; et al. Developing lipophilic aromatic halogenated fused systems with specific ring orientations, leading to potent anticancer analogs and targeting the c-Src Kinase enzyme. J. Mol. Struct. 2019, 1186, 212–223. [Google Scholar] [CrossRef]
  22. El-Agrody, A.M.; El-Mawgoud, H.K.A.; Fouda, A.M.; Khattab, E.S.A.E.H. Synthesis, in-vitro cytotoxicity of 4H-benzo[h]chromene derivatives and structure–activity relationships of 4-aryl group and 3-, 7-positions. Chem. Pap. 2016, 70, 1279–1292. [Google Scholar] [CrossRef]
  23. Halawa, A.H.; Elaasser, M.M.; El Kerdawy, A.M.; El-Hady, A.M.A.I.; Emam, H.A.; El-Agrody, A.M. Anticancer activities, molecular docking and structure–activity relationship of novel synthesized 4H-chromene, and 5H-chromeno 5H-chromeno[2,3-d]pyrimidine candidates. Med. Chem. Res. 2017, 26, 2624–2638. [Google Scholar] [CrossRef]
  24. El-Agrody, A.M.; Fouda, A.M.; Khattab, E.S.A.E.H. Halogenated 2-amino-4H-benzo[h]chromene derivatives as antitumor agents and the relationship between lipophilicity and antitumor activity. Med. Chem. Res. 2017, 26, 691–700. [Google Scholar] [CrossRef]
  25. Halawa, A.H.; Fouda, A.M.; Al-Dies, A.A.M.; El-Agrody, A.M. Synthesis, Biological Evaluation and Molecular Docking Studies of 4H-benzo [h]chromenes, 7H-benzo [h]chromeno [2, 3-d] pyrimidines as Antitumor Agents. Lett. Drug Des. Discov. 2016, 13, 77–88. [Google Scholar] [CrossRef]
  26. El-Mawgoud, H.K.A.; Fouda, A.M.; El-Nassag, M.A.A.; Elhenawy, A.A.; Alshahrani, M.Y.; El-Agrody, A.M. Discovery of novel rigid analogs of 2-naphthol with potent anticancer activity through multi-target topoisomerase I & II and tyrosine kinase receptor EGFR & VEGFR-2 inhibition mechanism. Chem. Biol. Interact. 2022, 355, 109838. [Google Scholar]
  27. El Gaafary, M.; Lehner, J.; Fouda, A.M.; Hamed, A.; Ulrich, J.; Simmet, T.; Syrovets, T.; El-Agrody, A.M. Synthesis and evaluation of antitumor activity of 9-methoxy-1H-benzo[f]chromene derivatives. Bioorg. Chem. 2021, 116, 105402. [Google Scholar] [CrossRef]
  28. Elgaafary, M.; Fouda, A.M.; Mohamed, H.M.; Hamed, A.; El-Mawgoud, H.K.; Jin, L.; Ulrich, J.; Simmet, T.; Syrovets, T.; El-Agrody, A.M. Synthesis of β-enaminonitriles linked 8-methoxy-1H-benzo[f]chromene moieties and analysis of their antitumor mechanisms. Front. Chem. 2021, 9, 759149. [Google Scholar] [CrossRef]
  29. Fouda, A.M.; Okasha, R.M.; Alblewi, F.F.; Mora, A.; Afifi, T.H.; El-Agrody, A.M. A proficient microwave synthesis with structure elucidation and the exploitation of the biological behavior of the newly halogenated 3-amino-1H-benzo[f]chromene molecules, targeting dual inhibition of topoisomerase II and microtubules. Bioorg. Chem. 2020, 95, 103549. [Google Scholar] [CrossRef]
  30. Fouda, A.M.; Assiri, M.A.; Mora, A.; Ali, T.E.; Afifi, T.H.; El-Agrody, A.M. Microwave synthesis of novel halogenated β-enaminonitriles linked 9-bromo-1H-benzo[f]chromene moieties: Induces cell cycle arrest and apoptosis in human cancer cells via dual inhibition of topoisomerase I and II. Bioorg. Chem. 2019, 93, 103289. [Google Scholar] [CrossRef]
  31. El-Agrody, A.M.; Fouda, A.M.; Assiri, M.A.; Mora, A.; Ali, T.E.; Alam, M.M.; Alfaifi, M.Y. In vitro anticancer activity of pyrano[3, 2-c]chromene derivatives with both cell cycle arrest and apoptosis induction. Med. Chem. Res. 2020, 29, 617–629. [Google Scholar] [CrossRef]
  32. Fouda, A.M.; Youssef, A.M.S.; Afifi, T.H.; Mora, A.; El-Agrody, A.M. Cell cycle arrest and induction of apoptosis of newly synthesized pyranoquinoline derivatives under microwave irradiation. Med. Chem. Res. 2019, 28, 668–680. [Google Scholar] [CrossRef]
  33. Alblewi, F.F.; Okasha, R.M.; Eskandrani, A.A.; Afifi, T.H.; Mohamed, H.M.; Halawa, A.H.; Fouda, A.M.; Al-Dies, A.-A.M.; Mora, A.; El-Agrody, A.M. Design and synthesis of novel heterocyclic-based 4H-benzo[h]chromene moieties: Targeting antitumor caspase 3/7 activities and cell cycle analysis. Molecules 2019, 24, 1060. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  34. Cravotto, G.; Carnaroglio, D. Microwave Chemistry; De Gruyter: Berlin, Germany; Boston, MA, USA, 2017; p. 9873110479928. [Google Scholar]
  35. Tierney, J.P.; Lidström, P. Microwave Assisted Organic Synthesis; Blackwell Publishing: Oxford, UK, 2005. [Google Scholar]
  36. Amariucai-Mantu, D.; Mangalagiu, V.; Danac, R.; Mangalagiu, I.I. Microwave assisted reactions of Azahetero-cycles formedicinal chemistry applications. Molecules 2020, 25, 716. [Google Scholar] [CrossRef] [Green Version]
  37. El-Agrody, A.M.; Al-Dies, A.-A.M.; Fouda, A.M. Microwave assisted synthesis of 2-amino-6-methoxy-4H-benzo [h] chromene derivatives. Eur. J. Chem. 2014, 5, 133–137. [Google Scholar]
  38. Raimondi, M.V.; Randazzo, O.; Franca, M.; La Barone, G.; Vignoni, E.; Rossi, D.; Collina, S. Inhibitors, Reading the past for discovering novel anticancer agents. Molecules 2019, 24, 1140. [Google Scholar] [CrossRef] [Green Version]
  39. Srinivasan, B.; Tonddast-Navaei, S.; Roy, A.; Zhou, H.; Skolnick, J. Chemical space of Escherichia coli dihydrofolate reductase inhibitors: New approaches for discovering novel drugs for old bugs. Med. Res. Rev. 2019, 39, 684–705. [Google Scholar] [CrossRef]
  40. Sanad, S.M.; Mekky, A.E.; El-Idreesy, T.T. Potential bacterial biofilm, MRSA, and DHFR inhibitors based on new morpholine-linked chromene-thiazole hybrids: One-pot synthesis and in silico study. J. Mol. Struct. 2022, 1248, 131476. [Google Scholar] [CrossRef]
  41. Halawa, A.H.; Elgammal, W.E.; Hassan, S.M.; Hassan, A.H.; Nassar, H.S.; Ebrahim, H.Y.; Mehany, A.B.; El-Agrody, A.M. Synthesis, anticancer evaluation and molecular docking studies of new heterocycles linked to sulfonamide moiety as novel human topoisomerase types I and II poisons. Bioorg. Chem. 2020, 98, 103725. [Google Scholar] [CrossRef]
  42. Al-Sehemi, A.G.; Irfan, A.; El-Agrody, A. Synthesis, characterization and DFT study of 4H-benzo[h]chromene derivatives. J. Mol. Struct. 2012, 1018, 171–175. [Google Scholar] [CrossRef]
  43. Sayed, A.Z.; El-Hady, N.A.; El-Agrody, A.M. Condensation of α-cyanocinnamonitriles with 6-bromo-2-naphthol: Synthesis of pyrano [2,3-d]pyrimidine and pyrano [3,2-e][1,2,4] triazolo [2,3-c] pyrimidine derivatives. J. Chem. Res. 2000, 2000, 164–166. [Google Scholar] [CrossRef]
  44. El-Agrody, A.M.; El-Latif, M.A.; Fakery, A.H.; Bedair, A.H. Heteroaromatization with 4-hydroxycoumarin Part I: Synthesis of some new pyranocoumarins and coumarinopyranopyrimidines. J. Chem. Res. 2000, 2000, 26–27. [Google Scholar] [CrossRef]
  45. El-Agrody, A.M.; Khattab, E.S.A.E.H.; Fouda, A.M.; Al-Ghamdi, A.M. Synthesis and antitumor activities of certain novel 2-amino-9-(4-halostyryl)-4H-pyrano[3,2-h]quinoline derivatives. Med. Chem. Res. 2012, 21, 4200–4213. [Google Scholar] [CrossRef]
  46. El-Wahab, A.H.A.; Mohamed, H.; El-Agrody, A.M.; El-Nassag, M.A.; Bedair, A.H. Synthesis and Biological Screening of 4-Benzyl-2H-phthalazine Derivatives. Pharmaceuticals 2011, 4, 1158–1170. [Google Scholar] [CrossRef] [Green Version]
  47. Abd-El-Aziz, A.S.; Shipman, P.O.; Neeland, E.G.; Corkery, T.C.; Mohammed, S.; Harvey, P.D.; Mohamed, H.M.; Bedair, A.H.; El-Agrody, A.M.; Aguiar, P.M.; et al. Benzo [f]-and Benzo [h] Coumarin-Containing Poly (methyl methacrylate) s and Poly(methyl methacrylate) s with Pendant Coumarin-Containing Azo Dyes. Macromol. Chem. Phys. 2008, 209, 84–103. [Google Scholar] [CrossRef]
  48. El-Agrody, A.M.; Ali, F.M.; Eid, F.A.; El-Nassag, M.A.A.; El-Sherbeny, G.; Bedair, A.H. Synthesis and Antimicrobial Activity of Thioxopyrimidines and Related Derivatives. Phosphorus Sulfur Silicon Relat. Elem. 2006, 181, 839–864. [Google Scholar] [CrossRef]
  49. Bedair, A.H.; Aly, F.M.; El-Agrody, A.M.; Eid, F.A.; El-Nassag, M.A.A.; El-Sherbeny, G.M. Preparation and Antimicrobial Activity of p-Aminophenylacetic acid Derivatives: Synthesis of Carboxymethylphenylazopyrazoles, (Pyrazolo[3,4-e][1,2,4]triazin-2-yl)phenylacetic acid, (1H-benzo[d]imidazol-2-yl and Oxo-4H-benzo[d][1,3] (oxazin-2-yl)- methylphenyl-isoindoline-1,3-dione Derivatives. Acta Pharm. 2006, 56, 273–284. [Google Scholar]
  50. El-Agrody, A.M.; Hassan, S.M. Activated Nitriles in Heterocyclic Synthesis: Synthesis of Several New 2-Substituted Pyrano[1,2,4]Triazolopyrimidine Derivatives. J. Chem. Res. Synop. 1997, 9, 320–321. [Google Scholar] [CrossRef]
  51. El-Agrody, A.M. Activated nitriles in heterocyclic synthesis: Synthesis of several new naphtho[2,1-b] pyran-3-one derivatives. J. Chem. Res. Synop. 1994, 1, 50–51. [Google Scholar] [CrossRef]
  52. Omar, A.M.; Bajorath, J.; Ihmaid, S.; Mohamed, H.M.; El-Agrody, A.M.; Mora, A.; El-Araby, M.E.; Ahmed, H.E.A. Novel molecular discovery of promising amidine-based thiazole analogues as potent dual Matrix Metalloproteinase-2 and 9 inhibitors: Anticancer activity data with prominent cell cycle arrest and DNA fragmentation analysis effects. Bioorg. Chem. 2020, 101, 103992. [Google Scholar] [CrossRef]
  53. Halawa, A.H.; El-Gilil, S.M.A.; Bedair, A.H.; Eliwa, E.M.; Frese, M.; Sewald, N.; Shaaban, M.; El-Agrody, A.M. Synthesis of diverse amide linked bis-indoles and indole derivatives bearing coumarin-based moiety: Cytotoxicity and molecular docking investigations. Med. Chem. Res. 2018, 27, 796–806. [Google Scholar] [CrossRef]
  54. Eliwa, E.M.; Abdel-Razek, A.S.; Frese, M.; Wibberg, D.; Halawa, A.H.; El-Agrody, A.M.; Bedair, A.H.; Kalinowski, J.; Sewald, N.; Shaaban, M. New bioactive compounds from the marine-derived actinomycete Nocardiopsis lucentensis sp. ASMR2. Z. Nat. B 2017, 72, 351–360. [Google Scholar] [CrossRef]
  55. El-Agrody, A.M.; Afifi, T.H. The Reactivity of 8-Hydroxyquinoline and Its Derivatives Toward α-Cyanocinnamo-nitriles and Ethyl α-Cyanocinnamates: Synthesis, Reactions, and Applications of 4H-Pyrano[3,2-h]quinoline Derivatives. Heterocycles 2014, 89, 1557–1584. [Google Scholar] [CrossRef]
  56. Halawa, A.H.; Eliwa, E.M.; Hassan, A.A.; Nassar, H.S.; El-Eisawy, R.A.; Ismail, M.; Frese, M.; Shaaban, M.; El-Agrody, A.M.; Bedair, A.H.; et al. Synthesis, in vitro cytotoxicity activity against the human cervix carcinoma cell line and in silico computational predictions of new 4-arylamino-3-nitrocoumarin analogues. J. Mol. Struct. 2020, 1200, 127047. [Google Scholar] [CrossRef]
  57. Mohamed, H.M.; Fouda, A.M.; Khattab, E.S.A.E.H.; Agrody, A.M.; Afifi, T.H. Synthesis, in vitro cytotoxicity of 1H-benzo[f]chromene derivatives and structure-activity relationships of the 1-aryl group and 9-position. Z. Naturforsch. C J. Biosci. 2017, 72, 161–171. [Google Scholar] [CrossRef]
  58. Bedair, A.H.; Ali, F.M.; El-Agrody, A.M.; Eid, F.A.; El-Nassag, M.A.A.; El-Sherbeny, G. Preparation of 4-aminophenylacetic acid derivatives with promising antimicrobial activity. Acta Pharm. 2006, 56, 273–284. [Google Scholar]
  59. Allen, F.H.; Kennard, O.; Watson, D.G.; Brammer, L.; Orpen, A.G.; Taylor, R. Tables of Bond Lengths determined by X-Ray and Neutron Diffraction Part. J. Chem. Soc. Perkins Trans. 1987, 2, 1–19. [Google Scholar] [CrossRef]
  60. Dilution, A. European Committee for Antimicrobial Susceptibility Testing (EUCAST) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID: Determination of minimum inhibitory concentrations (MICs) of antibacterial agents by agar dilution. Clin. Microbiol. Infect. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis. 2000, 6, 509–515. [Google Scholar]
  61. French, G.L. Bactericidal agents in the treatment of MRSA infections—the potential role of daptomycin. J. Antimicrob. Chemother. 2006, 58, 1107–1117. [Google Scholar] [CrossRef] [Green Version]
  62. Bolin, J.T.; Filman, D.J.; Matthews, D.A.; Hamlin, R.C.; Kraut, J. Crystal structures of Escherichia coli and Lactobacillus casei dihydrofolate reductase refined at 1.7 A resolution. I. General features and binding of methotrexate. J. Biol. Chem. 1982, 257, 13650–13662. [Google Scholar] [CrossRef]
  63. Zhang, X.; Zhou, X.; Kisliuk, R.L.; Piraino, J.; Cody, V.; Gangjee, A. Design, synthesis, biological evaluation and X-ray crystal structure of novel classical 6,5,6-tricyclic benzo 4,5 thieno 2,3-d pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors. Bioorg. Med. Chem. 2011, 19, 3585–3594. [Google Scholar] [CrossRef] [PubMed]
  64. Rao, M.S.; Chhikara, B.S.; Tiwari, R.; Shirazi, A.N.; Parang, K.; Kumara, A. A Greener Synthesis of 2-Aminochromenes in Ionic Liquid and Evaluation of Their Antiproliferative Activities. Chem. Biol. Interface 2012, 2, 362–372. [Google Scholar]
  65. Lee, C.K.; Huang, H.W.; Lin, I.J.B. Simple amphiphilic liquid crystalline N-alkylimidazolium salts. A new solvent system providing a partially ordered environmentCrystal data for [C14H29-imH][NO3]: C17H33N3O3, M = 303.44, triclinic, a = 8.962 (3), b = 19.793 (18), c = 22.363 (7) Å, α = 99.606 (17), β = 92.371 (18), γ = 98.307 (18)°, V = 3862 (2) Å3, T = 298 K, space group P1 [combining macron], Z = 10, μ = 0.090 mm−1, σcalcd = 1.305 mg m−3, 1.52 <θ <25.00. Of 16247 reflections measured, 13442 were unique. Data were collected on a Siemens P4 diffractometer with graphite monochromatized Mo-Kα radiation (λ = 0.71073 Å) in ω scan mode. The structure was solved by direct methods and refined (based on F2 using all independent data) by full matrix least squares methods (Siemens SHELXTL V. 5.03). Chem. Commun. 2000, 19, 1911–1912. [Google Scholar]
  66. Siemens Analytical X-Ray Instruments. Inc. Anal. Chem. 1990, 62, 413A. [Google Scholar] [CrossRef]
  67. Frisch, M.J.; Trucks, G.W.; Schlegel, H.B.; Scuseria, G.E.; Robb, M.A.; Cheeseman, J.R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G.A.; et al. Gaussian 09, Revision, D. 01, Gaussian, Inc., Wallingford CT, 2013 Search PubMed;(b) AD Becke. J. Chem. Phys. 1993, 5648, 785–789. [Google Scholar]
  68. Alzahrani, A.S.; Nazreen, S.; Elhenawy, A.A.; Neamatallah, T.; Alam, M.M. Synthesis, Biological Evaluation, and Molecular Docking of New Benzimidazole-1, 2, 3-Triazole Hybrids as Antibacterial and Antitumor Agents. Polycycl. Aromat. Compd. 2022, 1–12. [Google Scholar] [CrossRef]
  69. Alam, M.M.; Malebari, A.M.; Syed, N.; Neamatallah, T.; Almalki, A.S.; Elhenawy, A.A.; Obaid, R.J.; Alsharif, M.A. Design, synthesis and molecular docking studies of thymol based 1, 2, and 3-triazole hybrids as thymidylate synthase inhibitors and apoptosis inducers against breast cancer cells. Bioorganic Med. Chem. 2021, 38, 116136. [Google Scholar] [CrossRef]
Crystals 12 00982 sch001 550
Scheme 1. Synthesis of 3-amino-1-(4-chlorophenyl)-9-methoxy-1H-benzo[f]Chromene-2-carbonitrile (4).
Scheme 1. Synthesis of 3-amino-1-(4-chlorophenyl)-9-methoxy-1H-benzo[f]Chromene-2-carbonitrile (4).
Crystals 12 00982 sch001
Crystals 12 00982 g001 550
Figure 1. ORTEP diagrams of the titled compound 4. Displacement ellipsoids are plotted at the 40% probability level for non-H atoms.
Figure 1. ORTEP diagrams of the titled compound 4. Displacement ellipsoids are plotted at the 40% probability level for non-H atoms.
Crystals 12 00982 g001
Crystals 12 00982 g002 550
Figure 2. Molecular packing of compound 4. Hydrogen bonds are drawn as dashed lines.
Figure 2. Molecular packing of compound 4. Hydrogen bonds are drawn as dashed lines.
Crystals 12 00982 g002
Crystals 12 00982 g003 550
Figure 3. Predicted binding mode of compounds 4 and reference inhibitors into 4DFR H-bondings represented in blue lines, while π-π bond in green line.
Figure 3. Predicted binding mode of compounds 4 and reference inhibitors into 4DFR H-bondings represented in blue lines, while π-π bond in green line.
Crystals 12 00982 g003
Crystals 12 00982 g004 550
Figure 4. Predicted binding mode of compounds 4 and reference inhibitors into 3NTZ H-bondings represented in blue lines, while π-π bond in green line.
Figure 4. Predicted binding mode of compounds 4 and reference inhibitors into 3NTZ H-bondings represented in blue lines, while π-π bond in green line.
Crystals 12 00982 g004
Table
Table 1. X-ray experimental details for compound 4.
Table 1. X-ray experimental details for compound 4.
Crystal Data
Chemical formulaC21H15ClN2O2
Mr362.80
Crystal system, space groupTriclinic, P-1
Temperature (K)293
a, b, c (Å)8.7171 (4), 10.9509 (5), 19.5853 (9)
α, β, γ (°)78.249 (2), 89.000 (2), 70.054 (2)
V (Å3)1717.88 (14)
Z4
Radiation typeCu Kα
µ (mm−1)2.12
Crystal size (mm)0.22 × 0.14 × 0.12
Data collection
DiffractometerBruker APEX-II D8 venture diffractometer
Absorption correctionMulti-scan
SADABS Bruker 2018
Tmin, Tmax0.901, 0.937
No. of measured, independent and observed [I > 2σ(I)] reflections15,845, 5040, 2471
Rint0.044
Refinement
R[F2 > 2σ(F2)], wR(F2), S0.107, 0.308, 1.26
No. of reflections5040
No. of parameters471
Δρmax, Δρmin (e Å−3)0.53, −0.33
CCDC No.2,054,799
Table
Table 2. Hydrogen-bond geometry (Å, °) for compound 4.
Table 2. Hydrogen-bond geometry (Å, °) for compound 4.
D—H···AD—HH···AD···AD—H···A
N1A—H1AA•••N2A i0.8602.39003.153 (14)149.00
N1A—H1AB•••O1B0.8602.50003.353 (12)170.00
N1B—H1BA•••N2B ii0.8602.38003.188 (15)156.00
N1B—H1BB•••O1A0.8602.42003.272 (12)171.00
Symmetry codes: i: x, y + 1, z; ii: −x + 3, −y−2, −z + 2.
Table
Table 3. Antimicrobial screening for compound 4.
Table 3. Antimicrobial screening for compound 4.
Diameter of Inhibition Zone (mm)
Gram + ve bacteriaGram − ve bacteria Fungi
CompoundS. aureusB. subtilisS. epid.E. cloacaE. coliS. typhi.A. fumigatesA. flavusC. Albicans
422 ± 0.726 ± 0.625 ± 0.426 ± 0.413 ± 0.116 ± 0.515 ± 1.116 ± 1.221 ± 0.7
Ampicillin24 ± 1.126 ± 1.028 ± 1.4------
Gentamycin---27 ± 0.630 ± 1.517 ± 0.4---
Ketoconazole------17 ± 1.216 ± 1.120 ± 0.2
Diameter of the hole = 6 mm; Data are expressed in the form of mean ± SD. Not active (<8 mm), Weak activity (8–12 mm), Moderate activity (13–16 mm), Strong activity (≥17 mm). Solvent: DMSO (8 mm).
Table
Table 4. The MIC (MBC/MIc) in μg/mL of compound 4.
Table 4. The MIC (MBC/MIc) in μg/mL of compound 4.
Gram + ve bacteriaGram − ve bacteriaFungi
CompoundS. aureusB. subtilisS. epid.E. cloacaE. coliS. typhi.A. fumigatesA. flavusC. Albicans
46.25 (12.5)12.5 (25)25 (50)25 (50)25 (100)50 (100)6.25 (12.5)12.5 (25)25 (100)
Ampicillin6.256.256.25------
Gentamycin---12.56.2512.5---
Ketoconazole------6.2512.56.25
Table
Table 5. The binding-affinity for tested compounds 4 with docking score (kcal/mol) against hDHFR.
Table 5. The binding-affinity for tested compounds 4 with docking score (kcal/mol) against hDHFR.
4DFR3NTZ
ΔErmsdH.BInt.E_eleΔErmsdH.BInt.E_ele
4−7.530.93−36.95−28.96−24.33−9.340.52−203.47−26.13−11.01
Methotrexate−8.821.90−21.08−20.66−56.52−6.792.28−21.52−31.78−9.75
Ampicillin−7.191.6974.28−21.28−13.81−7.441.7372.46−21.70−11.83
Gentamicin−8.272.93313.10−2.70−19.63−9.272.66212.67−21.96−14.70
Ketoconazole−7.532.3223.93−22.05−10.80−8.452.4030.81−14.48−8.75
ΔE: Free binding energy of the ligand, Int.: Affinity binding energy of hydrogen bond interaction with receptor, H.B.: Hydrogen bonding energy between protein and ligand. E_ele: Electrostatic interaction with the receptor.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Okasha, R.M.; Fouda, A.M.; Bajaber, M.A.; Ghabbour, H.A.; E. Amr, A.E.-G.; Naglah, A.M.; Almehizia, A.A.; Elhenawy, A.A.; El-Agrody, A.M. The Crystal Structure of 3-Amino-1-(4-Chlorophenyl)-9-Methoxy-1H-Benzo[f]Chromene-2-Carbonitrile: Antimicrobial Activity and Docking Studies. Crystals 2022, 12, 982. https://doi.org/10.3390/cryst12070982

AMA Style

Okasha RM, Fouda AM, Bajaber MA, Ghabbour HA, E. Amr AE-G, Naglah AM, Almehizia AA, Elhenawy AA, El-Agrody AM. The Crystal Structure of 3-Amino-1-(4-Chlorophenyl)-9-Methoxy-1H-Benzo[f]Chromene-2-Carbonitrile: Antimicrobial Activity and Docking Studies. Crystals. 2022; 12(7):982. https://doi.org/10.3390/cryst12070982

Chicago/Turabian Style

Okasha, Rawda M., Ahmed M. Fouda, Majed A. Bajaber, Hazem A. Ghabbour, Abd El-Galil E. Amr, Ahmed M. Naglah, Abdulrahman A. Almehizia, Ahmed A. Elhenawy, and Ahmed M. El-Agrody. 2022. "The Crystal Structure of 3-Amino-1-(4-Chlorophenyl)-9-Methoxy-1H-Benzo[f]Chromene-2-Carbonitrile: Antimicrobial Activity and Docking Studies" Crystals 12, no. 7: 982. https://doi.org/10.3390/cryst12070982

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop