Molecular Docking and Molecular Dynamics Simulations of Synthesized Thiazole‐Isatin‐1,2,3‐triazole Hybrids as Promising Inhibitors for DNA Gyrase and 14α‐Sterol Demethylase

In the present work, a new class of thiazole‐isatin‐1,2,3‐triazole hybrids ( 5 a – 5 p ) and precursor alkyne hybrids ( 6 a – 6 d ) has been reported with their in‐silico studies. After structural identifications using different spectroscopic technique such as FTIR, 1 H and 13 C NMR and HRMS, the synthesized hybrids were explored for their biological potential using molecular docking and molecular dynamics calculations. Molecular docking results revealed that compound 5 j showed maximum binding energy i. e. −10.3 and −12.6 kcal/mol against antibacterial and antifungal enzymes; 1KZN ( E. coli ) and 5TZ1 ( C. albicans ), respectively. Molecular dynamics simulations for the best molecule (100 ns) followed by PBSA calculations suggested a stable complex of 5 j with 5TZ1 with binding energy of −118.760 kJ/mol as compared to 1KZN (−94.593 kJ/mol). The mean RMSD values for the 1KZN with 5 j complex remained approximately 0.175 nm throughout all the time span of 100 ns in the production stages and is in the acceptable range. Whereas, 5TZ1 with 5 j complex, RMSD values exhibited variability within the range of 0.15–0.25 nm.