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

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.