In Silico Investigation of Quinazoline-Thiazole Hybrids as Dual DNA Gyrase and Sterol 14-α Demethylase Inhibitors: Molecular Docking, ADMET Profiling, and SAR Studies

In the quest of novel antimicrobial agents to combat resistance, a series of quinazoline-thiazole derivatives (3a-3j) were synthesized and subjected to computational evaluation. This article covers the in-silico investigations and SAR studies of the synthesized compounds. The in silico molecular docking of these compounds were carried out against bacterial target E. coli DNA Gyrase B (PDB: 1NJI) and fungal target Sterol 14-α demethylase (PDB: 5W3F). Docking simulations revealed that the synthesized hybrids exhibit superior binding affinity compared to standard drugs, with compound 3h showing the highest affinity for 1NJI (-10.1 Kcal/mol) and compound 3d showing the highest affinity for 5W3F (-8.6 Kcal/mol). ADMET predictions indicate favourable drug-likeness, with most compounds adhering to Lipinski’s Rule of Five. These computational findings correlate well with in vitro antimicrobial evaluations, suggesting that the quinazoline-thiazole scaffold is a promising lead for dual-action antimicrobial development.