A New Family of Benzo[h]Chromene Based Azo Dye: Synthesis, In-Silico and DFT Studies with In Vitro Antimicrobial and Antiproliferative Assessment
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis and Characterization
2.2. UV–Visible and Halochromism Studies
2.3. Calculated Frontier Molecular Orbitals (FMOs)
2.4. Biological Screening
2.4.1. Antimicrobial Screening
2.4.2. Cytotoxic Screening
2.5. Computational Studies and SAR Analysis
2.5.1. Docking Studies
2.5.2. Molecular Descriptors-Based SAR (Structure–Activity Relationship) Analysis
3. Materials and Methods
3.1. Materials and Instrumentation
3.2. Biological Studies
3.2.1. Antimicrobial Screening
3.2.2. Cytotoxic Screening
3.3. Molecular Modeling
3.4. Computational Methods and Calculations
3.5. Synthesis
3.5.1. General Procedure for the Synthesis of 2-Amino-6-(4-Ethoxyphenylazo)-4(-Phenyl)-4H-Benzo[h]Chromene Derivatives
3.5.2. 2-Amino-6-(4-Ethoxyphenylazo)-4-(2-Fluoro-Phenyl)-4H-Benzo[h]Chromene-3-Carbonitrile (4a)
3.5.3. 2-Amino-6-(4-Ethoxyphenylazo)-4-(2-Chloro-Phenyl)-4H-Benzo[h]Chromene-3-Carbonitrile (4b)
3.5.4. 2-Amino-6-(4-Ethoxyphenylazo)-4-(2-Bromo-Phenyl)-4H-Benzo[h]Chromene-3-Carbonitrile (4c)
3.5.5. 2-Amino-6-(4-Ethoxyphenylazo)-4-(3-Bromo-Phenyl)-4H-Benzo[h]Chromene-3-Carbonitrile (4d)
3.5.6. 2-Amino-6-(4-Ethoxyphenylazo)-4-(3-Chloro-Phenyl)-4H-Benzo[h]Chromene-3-Carbonitrile (4e)
3.5.7. 2-Amino-6-(4-Ethoxyphenylazo)-4-(4-Fluoro-Phenyl)-4H-Benzo [h] Chromene-3-Carbonitrile (4f)
3.5.8. 2-Amino-6-(4-Ethoxyphenylazo)-4-(3-Nitro-Phenyl)-4H-Benzo[h]Chromene-3-Carbonitrile (4g)
3.5.9. Ethyl-2-Amino-6-(4-Ethoxyphenylazo)-4-(2-Bromo-Phenyl)-4H-Benzo[h]Chromene -3-Carboxylate (4h)
3.5.10. Ethyl-2-Amino-6-(4-Ethoxyphenylazo)-4-(2-Chloro-Phenyl)-4H-Benzo[h]Chromene -3-Carboxylate (4i)
3.5.11. Ethyl-2-Amino-6-(4-Ethoxyphenylazo)-4-(3-Bromo-Phenyl)-4H-Benzo[h]Chromene-3-Carboxylate (4j)
3.5.12. Ethyl-2-Amino-6-(4-Ethoxyphenylazo)-4-(3-Nitro-Phenyl)-4H-Benzo[h]Chromene-3-Carboxylate (4k)
3.5.13. Ethyl-2-Amino-6-(4-Ethoxyphenylazo)-4-(4-Fluoro-Phenyl)-4H-Benzo[h]Chromene-3-Carboxylate (4l)
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound | HOMO | LUMO | ΔELUMO-HOMO | λmax (Theo) |
---|---|---|---|---|
4a | −5.76 | −2.51 | 3.25 | 381.95 |
4b | −5.78 | −2.54 | 3.24 | 382.65 |
4c | −5.77 | −2.53 | 3.24 | 382.97 |
4d | −5.83 | −2.60 | 3.23 | 383.45 |
4e | −5.84 | −2.61 | 3.23 | 383.42 |
4f | −5.83 | −2.60 | 3.23 | 383.74 |
4g | −5.93 | −3.01 | 2.92 | 424.23 |
4h | −5.65 | −2.41 | 3.25 | 381.64 |
4i | −5.66 | −2.41 | 3.25 | 381.54 |
4j | −5.73 | −2.48 | 3.24 | 382.21 |
4k | −5.84 | −2.90 | 2.94 | 421.93 |
4l | −5.60 | −2.38 | 3.22 | 384.67 |
Inhibition Zone Diameter (mm) | ||||||||
---|---|---|---|---|---|---|---|---|
Compounds | Gram Positive | Gram Negative | Fungi | |||||
S.P. | B.S. | P.A. | E.C. | A.F. | S.R. | G.C. | C.A. | |
4a | 20.5 ± 0.44 | 22.4 ± 0.58 | NA | 19.4 ± 0.19 | 18.7 ± 0.25 | 15.6 ± 0.25 | 19.2 ± 0.58 | NA |
4b | 18.4 ± 0.34 | 21.5 ± 0.25 | NA | 20.4 ± 0.58 | 20.9 ± 0.63 | 19.2 ± 0.27 | 22.8 ± 0.35 | NA |
4c | 17.4 ± 0.34 | 20.2 ± 0.25 | NA | 17.7 ± 0.58 | 16.2 ± 0.63 | 17.1 ± 0.27 | 17.1 ± 0.35 | NA |
4d | 19.6 ± 0.55 | 20.5 ± 0.52 | NA | 15.9 ± 0.58 | 18.6 ± 0.36 | 17.3 ± 0.35 | 18.9 ± 0.44 | NA |
4e | 20.3 ± 0.44 | 20.9 ± 0.25 | NA | 15.4 ± 0.39 | 18.3 ± 0.55 | 20.1 ± 0.27 | 20.9 ± 0.58 | NA |
4f | 20.3 ± 0.28 | 21.4 ± 0.37 | NA | 16.9 ± 0.19 | 17.6 ± 0.11 | 18.4 ± 0.23 | 20.9 ± 0.27 | NA |
4g | 19.3 ± 0.16 | 20.3 ± 0.19 | NA | 18.9 ± 0.27 | 16.2 ± 0.20 | 20.8 ± 0.15 | 21.8 ± 0.18 | NA |
4h | 19.6 ± 0.52 | 21.4 ± 0.63 | NA | 19.3 ± 0.62 | 19.3 ± 0.62 | 20.4 ± 0.34 | 20.8 ± 0.64 | NA |
4i | 21.4 ± 0.25 | 23.4 ± 0.58 | NA | 21.3 ± 0.16 | 23.7 ± 0.26 | 21.4 ± 0.35 | 25.4 ± 0.18 | NA |
4j | 16.1 ± 0.55 | 18.6 ± 0.25 | NA | 13.4 ± 0.19 | 10.6 ± 0.44 | 18.7 ± 0.25 | 23.4 ± 0.58 | NA |
4k | 18.3 ± 0.19 | 20.3 ± 0.24 | NA | 17.7 ± 0.25 | NA | 15.4 ± 0.24 | 18.3 ± 0.15 | NA |
4l | 20.8 ± 0.34 | 22.6 ± 0.25 | NA | 18.2 ± 0.58 | 18.7 ± 0.63 | 16.3 ± 0.27 | 19.4 ± 0.35 | NA |
Ampicillin Gentamicin Amphotericin B | 21.9 ± 0.2 | 25.4 ± 0.3 | – | – | – | – | – | – |
– | – | 17.3 ± 0.1 | 19.9 ± 0.3 | – | – | – | – | |
– | – | – | – | 23.9 ± 0.1 | 19.7 ± 0.2 | 17.9 ± 0.2 | 19.8 ± 0.1 |
Minimal Inhibitory Concentration (MIC, µg/mL) | ||||||||
---|---|---|---|---|---|---|---|---|
Compounds | Gram Positive | Gram Negative | Fungi | |||||
S.P. | B.S. | P.A. | E.C. | A.F. | S.R. | G.C. | C.A. | |
4a | 1.95 | 0.98 | NA | 62.5 | 15.63 | 31.25 | 7.81 | NA |
4b | 7.81 | 1.95 | NA | 3.9 | 1.95 | 3.9 | 0.98 | NA |
4c | 3.9 | 1.95 | NA | 31.25 | 7.81 | 15.63 | 0.98 | NA |
4d | 3.9 | 15.63 | NA | 3.9 | 125 | 125 | 62.5 | NA |
4e | 62.5 | 31.25 | NA | 15.63 | 125 | 125 | 62.5 | NA |
4f | 7.81 | 7.81 | NA | 3.9 | 7.81 | 62.5 | 0.49 | NA |
4g | 3.9 | 3.9 | NA | 3.9 | 31.25 | 3.9 | 1.95 | NA |
4h | 0.98 | 1.95 | NA | 3.9 | 3.9 | 3.9 | 15.63 | NA |
4i | 1.95 | 0.98 | NA | 1.95 | 0.98 | 1.95 | 0.49 | NA |
4j | 7.81 | 7.81 | NA | 3.9 | 15.63 | 31.25 | 7.81 | NA |
4k | 1.95 | 0.49 | NA | 15.63 | NA | 62.5 | 7.81 | NA |
4l | 3.9 | 0.98 | NA | 7.81 | 7.81 | 31.25 | 3.9 | NA |
Ampicillin Gentamicin Amphotericin B | 0.49 | 0.06 | – | – | – | – | – | – |
– | – | 3.9 | 7.81 | – | – | – | – | |
– | – | – | – | 0.12 | 0.49 | 7.81 | 1.95 |
Compounds | IC50 (µg/mL) | ||
---|---|---|---|
HCT-116 | MCF-7 | HepG-2 | |
4a | 42.1 | 21.9 | 11.6 |
4b | 19.2 | 16.2 | 11.3 |
4c | 12.2 | 21.1 | 7.28 |
4d | 15.3 | 9.16 | 7.64 |
4e | 5.54 | 19.7 | 9.99 |
4f | 42.6 | 22.5 | 14.3 |
4g | 9.01 | 7.14 | 12.0 |
4h | 40.9 | 5.5 | 9.19 |
4i | 30.0 | 11.5 | 8.76 |
4j | 4.35 | 4.72 | 11.6 |
4k | 11.2 | 9.5 | 10.5 |
4l | 2.51 | 3.91 | 5.41 |
Doxorubicin | 0.88 | 1.02 | 1.19 |
Vinblastine | 2.6 | 6.1 | 4.6 |
Colchicine | 42.8 | 17.7 | 10.6 |
Compound No. | 4b | 4h | Fat Brown B | 1-(4-Ethoxyphenyl)-2-(4-Phenyl-4H-Benzo[h]Chromen-6-yl)Diazene | |
---|---|---|---|---|---|
Amino acid (Distance Å) | Asp 73 | -NH2 (2.3, 2.4) | – | --OH (2.4) | – |
Thr 165 | -CN (3.2) | – | – | – | |
Asn 46 | – | --NH2 (2.0) | – | – | |
Asp 49 | – | --Br (3.2) | – | – | |
Ile 78 | – | -phenyl | – | – | |
Interaction type | H-bonding | H-bonding (aromatic) | H-bonding | H-bonding | |
∆G (kcal/mol) (MOE) | −13.61 | −12.23 | −11.24 | – | |
∆G (kcal/mol) (Pyrx) | −9.0 | −8.6 | −7.7 | −7.9 |
Compounds | A = −ELUMO | I = −EHOMO | µ | ||||
---|---|---|---|---|---|---|---|
4a | 4.14 | 1.63 | 0.62 | 5.26 | 2.51 | 5.76 | 6.4 |
4b | 4.16 | 1.62 | 0.62 | 5.34 | 2.54 | 5.78 | 6.9 |
4c | 4.15 | 1.62 | 0.62 | 5.32 | 2.53 | 5.77 | 6.7 |
4d | 4.22 | 1.62 | 0.62 | 5.50 | 2.60 | 5.83 | 7.7 |
4e | 4.23 | 1.62 | 0.62 | 5.53 | 2.61 | 5.84 | 8.0 |
4f | 4.22 | 1.62 | 0.62 | 5.50 | 2.60 | 5.83 | 7.2 |
4g | 4.47 | 1.46 | 0.68 | 6.84 | 3.01 | 5.93 | 10.3 |
4h | 4.03 | 1.62 | 0.62 | 5.01 | 2.41 | 5.65 | 2.9 |
4i | 4.04 | 1.63 | 0.62 | 5.01 | 2.41 | 5.66 | 3.1 |
4j | 4.11 | 1.63 | 0.62 | 5.18 | 2.48 | 5.73 | 4.2 |
4k | 4.37 | 1.47 | 0.68 | 6.50 | 2.90 | 5.84 | 7.4 |
4l | 3.99 | 1.61 | 0.62 | 4.94 | 2.38 | 5.60 | 2.5 |
Compound | Lipophilicity | Polar Surface Area | H-Bond Acceptor | H-Bond Donor | Violations | Volume |
---|---|---|---|---|---|---|
4a | 6.57 | 93.01 | 6 | 2 | 1 | 407.77 |
4b | 7.08 | 93.01 | 6 | 2 | 1 | 416.38 |
4c | 7.21 | 93.01 | 6 | 2 | 2 | 420.73 |
4d | 7.24 | 93.01 | 6 | 2 | 2 | 420.73 |
4e | 7.11 | 93.01 | 6 | 2 | 1 | 416.38 |
4f | 6.62 | 93.01 | 6 | 2 | 1 | 407.77 |
4g | 6.62 | 93.01 | 6 | 2 | 1 | 407.77 |
4h | 6.39 | 138.84 | 9 | 2 | 1 | 426.17 |
4i | 7.67 | 95.52 | 7 | 2 | 2 | 465.20 |
4j | 7.54 | 95.52 | 7 | 2 | 2 | 460.85 |
4k | 7.69 | 95.52 | 7 | 2 | 2 | 465.20 |
4l | 6.84 | 141.35 | 10 | 2 | 2 | 470.64 |
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Abd-El-Aziz, A.S.; Alsaggaf, A.; Assirey, E.; Naqvi, A.; Okasha, R.M.; Afifi, T.H.; Hagar, M. A New Family of Benzo[h]Chromene Based Azo Dye: Synthesis, In-Silico and DFT Studies with In Vitro Antimicrobial and Antiproliferative Assessment. Int. J. Mol. Sci. 2021, 22, 2807. https://doi.org/10.3390/ijms22062807
Abd-El-Aziz AS, Alsaggaf A, Assirey E, Naqvi A, Okasha RM, Afifi TH, Hagar M. A New Family of Benzo[h]Chromene Based Azo Dye: Synthesis, In-Silico and DFT Studies with In Vitro Antimicrobial and Antiproliferative Assessment. International Journal of Molecular Sciences. 2021; 22(6):2807. https://doi.org/10.3390/ijms22062807
Chicago/Turabian StyleAbd-El-Aziz, Alaa S., Azhaar Alsaggaf, Eman Assirey, Arshi Naqvi, Rawda M. Okasha, Tarek H. Afifi, and Mohamed Hagar. 2021. "A New Family of Benzo[h]Chromene Based Azo Dye: Synthesis, In-Silico and DFT Studies with In Vitro Antimicrobial and Antiproliferative Assessment" International Journal of Molecular Sciences 22, no. 6: 2807. https://doi.org/10.3390/ijms22062807