In silico Investigation and Molecular Docking Studies of Pyrazole Incorporated Thiadiazole Derivatives for Antimicrobial Activities

Abstract

Background: In the current investigation, derivatives incorporating pyrazole and thiadiazole ring systems were designed, and docking studies were conducted to elucidate their potential binding mode. Antimicrobial Resistance (AMR) is a critical threat to global public health and development, recognized by the World Health Organization (WHO) as one of the top 10 risks worldwide. Objective: The objective was to develop new antimicrobial drugs that can effectively target a wide range of resistant microbes. Methods: The designed derivatives were docked using AutoDock Vina 4.2 against the active sites of Staphylococcus aureus DHFR (2W9H), Staphylococcus aureus GyrB (4URO), Staphylococcus aureus thymidylate kinase (4QGG) for antibacterial activity and Candida albicans DHFR (1M78), Candida albicans aspartic protease 2 (3PVK), Candida albicans N-myristoyl transferase (1IYK) for antifungal activity. Results: The designed derivatives underwent further assessment for in silico physicochemical properties, and drug-likeness. Conclusion: Several of the derivatives exhibited notable anti-microbial activity, demonstrating a potency on par with the Standard drug Ciprofloxacin and Fluconazole. The results, evaluated based on docking scores into the receptor's active site, suggested that the most active derivatives, W36 and W33, may act as promising antibacterial against 2W9H and antifungal against 1IYK, respectively.