Antimicrobial activity, synthesis, and docking study of some novel arylazo-1,3-thiazolopyrimidine and arylazo-1,3-thiazolopyridopyrimidine derivatives

Abstract In this study, a new series of aryl azo thiazolopyrimidine and thiazolopyridopyrimidine derivatives was synthesized using novel 6-aryl-4-(2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-9-yl)-3,4-dihydropyrimidine-2(1H)-thione and 5-aryl-7-(2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinoli...

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Main Authors: Jihan Qurban, Sara A. Alqarni, Adel I. Alalawy, Nawaa Ali H. Alshammari, Gadeer R. S. Ashour, Maryam M. Alnoman, Hanadi A. Katuah, Nashwa M. El-Metwaly
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Chemistry
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Online Access:https://doi.org/10.1186/s13065-025-01506-1
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author Jihan Qurban
Sara A. Alqarni
Adel I. Alalawy
Nawaa Ali H. Alshammari
Gadeer R. S. Ashour
Maryam M. Alnoman
Hanadi A. Katuah
Nashwa M. El-Metwaly
author_facet Jihan Qurban
Sara A. Alqarni
Adel I. Alalawy
Nawaa Ali H. Alshammari
Gadeer R. S. Ashour
Maryam M. Alnoman
Hanadi A. Katuah
Nashwa M. El-Metwaly
author_sort Jihan Qurban
collection DOAJ
description Abstract In this study, a new series of aryl azo thiazolopyrimidine and thiazolopyridopyrimidine derivatives was synthesized using novel 6-aryl-4-(2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-9-yl)-3,4-dihydropyrimidine-2(1H)-thione and 5-aryl-7-(2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-9-yl)-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-one scaffolds as key intermediates. Structural elucidation of all intermediates and final products was performed via IR, UV, 1H/13C-NMR, and mass spectrometry. Among the forty synthesized compounds, several exhibited significant in vitro antimicrobial activities, particularly derivatives 11a, 11b, 7a, and 7b, with potent inhibition against S. aureus, E. coli, and C. albicans. Molecular docking studies using the bacterial DNA gyrase B subunit (Protein Data Bank (PDB): 1aj6) revealed favorable binding interactions, especially for 11b, which demonstrated the best docking score and strong π–H interactions. Furthermore, DFT-based molecular modeling confirmed the stability and high electronic reactivity of selected bioactive compounds, with low HOMO–LUMO energy gaps and favorable electrostatic potential profiles. Structure–activity relationship (SAR) analysis indicated that electronic effects, lipophilicity, and heteroaromatic substitution patterns critically influence antimicrobial potency. These findings support the potential of thiazolopyridopyrimidine derivatives as promising scaffolds for future antimicrobial drug development.
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spelling doaj-art-e80c567ccb9341e5ab814d65a0b2ea8c2025-08-20T02:39:04ZengBMCBMC Chemistry2661-801X2025-05-0119112710.1186/s13065-025-01506-1Antimicrobial activity, synthesis, and docking study of some novel arylazo-1,3-thiazolopyrimidine and arylazo-1,3-thiazolopyridopyrimidine derivativesJihan Qurban0Sara A. Alqarni1Adel I. Alalawy2Nawaa Ali H. Alshammari3Gadeer R. S. Ashour4Maryam M. Alnoman5Hanadi A. Katuah6Nashwa M. El-Metwaly7Department of Chemistry, College of Science, Umm Al-Qura UniversityDepartment of Chemistry, College of Science, University of JeddahDepartment of Biochemistry, Faculty of Science, University of TabukDepartment of Chemistry, College of Science, Northern Border UniversityDepartment of Chemistry, College of Science, Umm Al-Qura UniversityBiology Department, Faculty of Science, Taibah UniversityDepartment of Chemistry, College of Science, Umm Al-Qura UniversityDepartment of Chemistry, College of Science, Umm Al-Qura UniversityAbstract In this study, a new series of aryl azo thiazolopyrimidine and thiazolopyridopyrimidine derivatives was synthesized using novel 6-aryl-4-(2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-9-yl)-3,4-dihydropyrimidine-2(1H)-thione and 5-aryl-7-(2,3,6,7-tetrahydro-1H,5H-pyrido[3,2,1-ij]quinolin-9-yl)-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-one scaffolds as key intermediates. Structural elucidation of all intermediates and final products was performed via IR, UV, 1H/13C-NMR, and mass spectrometry. Among the forty synthesized compounds, several exhibited significant in vitro antimicrobial activities, particularly derivatives 11a, 11b, 7a, and 7b, with potent inhibition against S. aureus, E. coli, and C. albicans. Molecular docking studies using the bacterial DNA gyrase B subunit (Protein Data Bank (PDB): 1aj6) revealed favorable binding interactions, especially for 11b, which demonstrated the best docking score and strong π–H interactions. Furthermore, DFT-based molecular modeling confirmed the stability and high electronic reactivity of selected bioactive compounds, with low HOMO–LUMO energy gaps and favorable electrostatic potential profiles. Structure–activity relationship (SAR) analysis indicated that electronic effects, lipophilicity, and heteroaromatic substitution patterns critically influence antimicrobial potency. These findings support the potential of thiazolopyridopyrimidine derivatives as promising scaffolds for future antimicrobial drug development.https://doi.org/10.1186/s13065-025-01506-1ChalconesPyrimidinethion derivativesAntibacterial activityMolecular docking
spellingShingle Jihan Qurban
Sara A. Alqarni
Adel I. Alalawy
Nawaa Ali H. Alshammari
Gadeer R. S. Ashour
Maryam M. Alnoman
Hanadi A. Katuah
Nashwa M. El-Metwaly
Antimicrobial activity, synthesis, and docking study of some novel arylazo-1,3-thiazolopyrimidine and arylazo-1,3-thiazolopyridopyrimidine derivatives
BMC Chemistry
Chalcones
Pyrimidinethion derivatives
Antibacterial activity
Molecular docking
title Antimicrobial activity, synthesis, and docking study of some novel arylazo-1,3-thiazolopyrimidine and arylazo-1,3-thiazolopyridopyrimidine derivatives
title_full Antimicrobial activity, synthesis, and docking study of some novel arylazo-1,3-thiazolopyrimidine and arylazo-1,3-thiazolopyridopyrimidine derivatives
title_fullStr Antimicrobial activity, synthesis, and docking study of some novel arylazo-1,3-thiazolopyrimidine and arylazo-1,3-thiazolopyridopyrimidine derivatives
title_full_unstemmed Antimicrobial activity, synthesis, and docking study of some novel arylazo-1,3-thiazolopyrimidine and arylazo-1,3-thiazolopyridopyrimidine derivatives
title_short Antimicrobial activity, synthesis, and docking study of some novel arylazo-1,3-thiazolopyrimidine and arylazo-1,3-thiazolopyridopyrimidine derivatives
title_sort antimicrobial activity synthesis and docking study of some novel arylazo 1 3 thiazolopyrimidine and arylazo 1 3 thiazolopyridopyrimidine derivatives
topic Chalcones
Pyrimidinethion derivatives
Antibacterial activity
Molecular docking
url https://doi.org/10.1186/s13065-025-01506-1
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