Next Article in Journal
Development of Naphthalene-Derivative Bis-QACs as Potent Antimicrobials: Unraveling Structure–Activity Relationship and Microbiological Properties
Previous Article in Journal
Effect of Different Colours of Light on Chosen Aspects of Metabolism of Radish Sprouts with Phosphoromic Approach
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Molecules
Volume 29
Issue 23
10.3390/molecules29235529
molecules-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:
This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Evaluation of Quinazolin-2,4-Dione Derivatives as Promising Antibacterial Agents: Synthesis, In Vitro, In Silico ADMET and Molecular Docking Approaches

by
Aboubakr H. Abdelmonsef
1,*,
Mohamed El-Naggar
2,
Amal O. A. Ibrahim
1,
Asmaa S. Abdelgeliel
3,
Ihsan A. Shehadi
2,
Ahmed M. Mosallam
1 and
Ahmed Khodairy
4
1
Department of Chemistry, Faculty of Science, South Valley University, Qena 83523, Egypt
2
Pure and Applied Chemistry Group, Chemistry Department, College of Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
3
Department of Botany and Microbiology, Faculty of Science, South Valley University, Qena 83523, Egypt
4
Department of Chemistry, Faculty of Science, Sohag University, Sohag 82524, Egypt
*
Author to whom correspondence should be addressed.
Molecules 2024, 29(23), 5529; https://doi.org/10.3390/molecules29235529
Submission received: 28 September 2024 / Revised: 18 November 2024 / Accepted: 19 November 2024 / Published: 22 November 2024
(This article belongs to the Section Organic Chemistry)
Review Reports Versions Notes

Abstract

Abstract: A series of new quinazolin-2,4-dione derivatives incorporating amide/eight-membered nitrogen-heterocycles 2a–c, in addition, acylthiourea/amide/dithiolan-4-one and/or phenylthiazolidin-4-one 3a–d and 4a–d. The starting compound 1 was prepared by reaction of 4-(2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-benzoyl chloride with ammonium thiocyanate and cyanoacetic acid hydrazide. The reaction of 1 with strong electrophiles, namely, o-aminophenol, o-amino thiophenol, and/or o-phenylene diamine, resulted in corresponding quinazolin-2,4-dione derivatives incorporating eight-membered nitrogen-heterocycles 2a–d. Compounds 3a–d and 4a–d were synthesized in good-to-excellent yield through a one-pot multi-component reaction (MCR) of 1 with carbon disulfide and/or phenyl isocyanate under mild alkaline conditions, followed by ethyl chloroacetate, ethyl iodide, methyl iodide, and/or concentrated HCl, respectively. The obtained products were physicochemically characterized by melting points, elemental analysis, and spectroscopic techniques, such as FT-IR, 1H-NMR, 13C-NMR, and MS. The antibacterial efficacy of the obtained eleven molecules was examined in vitro against two Gram-positive bacterial strains (Staphylococcus aureus and Staphylococcus haemolyticus). Furthermore, Computer-Aided Drug Design (CADD) was performed on the synthesized derivatives, standard drug (Methotrexate), and reported antibacterial drug with the target enzymes of bacterial strains (S. aureus and S. haemolyticus) to explain their binding mode of actions. Notably, our findings highlight compounds 2b and 2c as showing both the best antibacterial activity and docking scores against the targets. Finally, according to ADMET predictions, compounds 2b and 2c possessed acceptable pharmacokinetics properties and drug-likeness properties.
Keywords: quinazolin-2,4-dione; eight-membered nitrogen-heterocycles; dithiolan-4-one; phenyl-thiazolidin-4-one; antibacterial assessment; molecular docking quinazolin-2,4-dione; eight-membered nitrogen-heterocycles; dithiolan-4-one; phenyl-thiazolidin-4-one; antibacterial assessment; molecular docking

Share and Cite

MDPI and ACS Style

Abdelmonsef, A.H.; El-Naggar, M.; Ibrahim, A.O.A.; Abdelgeliel, A.S.; Shehadi, I.A.; Mosallam, A.M.; Khodairy, A. Evaluation of Quinazolin-2,4-Dione Derivatives as Promising Antibacterial Agents: Synthesis, In Vitro, In Silico ADMET and Molecular Docking Approaches. Molecules 2024, 29, 5529. https://doi.org/10.3390/molecules29235529

AMA Style

Abdelmonsef AH, El-Naggar M, Ibrahim AOA, Abdelgeliel AS, Shehadi IA, Mosallam AM, Khodairy A. Evaluation of Quinazolin-2,4-Dione Derivatives as Promising Antibacterial Agents: Synthesis, In Vitro, In Silico ADMET and Molecular Docking Approaches. Molecules. 2024; 29(23):5529. https://doi.org/10.3390/molecules29235529

Chicago/Turabian Style

Abdelmonsef, Aboubakr H., Mohamed El-Naggar, Amal O. A. Ibrahim, Asmaa S. Abdelgeliel, Ihsan A. Shehadi, Ahmed M. Mosallam, and Ahmed Khodairy. 2024. "Evaluation of Quinazolin-2,4-Dione Derivatives as Promising Antibacterial Agents: Synthesis, In Vitro, In Silico ADMET and Molecular Docking Approaches" Molecules 29, no. 23: 5529. https://doi.org/10.3390/molecules29235529

APA Style

Abdelmonsef, A. H., El-Naggar, M., Ibrahim, A. O. A., Abdelgeliel, A. S., Shehadi, I. A., Mosallam, A. M., & Khodairy, A. (2024). Evaluation of Quinazolin-2,4-Dione Derivatives as Promising Antibacterial Agents: Synthesis, In Vitro, In Silico ADMET and Molecular Docking Approaches. Molecules, 29(23), 5529. https://doi.org/10.3390/molecules29235529

Article Metrics

Back to TopTop