Investigating the antimicrobial and anti-inflammatory activities of novel thiophene derivatives by in-vitro studies, molecular docking, spectral analysis, and quantum chemical calculations

Abstract

The rise of antibiotic-resistant pathogens and the widespread occurrence of inflammatory diseases have raised considerable global health concerns. Consequently, there is a critical need to formulate novel and potent drug candidates to counteract these pressing global threats effectively. Hence, this study presents a comprehensive investigation involving spectral (FT-IR, and 1H NMR) analysis, experimental, molecular docking, and quantum chemical calculations employing density functional theory (DFT) to fully characterize and identify the synthesized compounds (Thiosemicarbazide Schiff base (TSB), 4‑methoxy aniline Schiff base (ASB), Phenyl urea Schiff base (PSB) at the ωB97XD/6-311++G(2d,2p) level of theory. Noteworthy observations from the antimicrobial investigations against four different microorganisms: Staphylococcus aureus, Escherichia coli, Candida albicans, and Aspergillus niger, TSB and ASB displayed varying degrees of antimicrobial activity. Notably, they exhibited the most significant effect against Candida albicans and A. niger, showing promise in combatting fungal infections. In contrast, PSB demonstrated moderate to high antimicrobial activity against E. coli, ranging from 15 mm to 24 mm. Molecular docking studies further confirmed TSB's strong binding affinity against Candida albicans with -6.4 kcal/mol, indicating robust interaction with the target protein. TSB also exhibited reasonably good binding affinities of -5.5 kcal/mol and -5.1 kcal/mol against Aspergillus niger and E. coli, respectively. ASB and PSB displayed particularly strong binding affinities against specific microorganisms, making them potential candidates for further investigation as antimicrobial agents. Furthermore, investigation into anti-inflammatory activity revealed that PSB demonstrated the highest free radical scavenging activity, with a percentage of 62.39 % and an IC50 value of 41.83. ASB followed with a free radical scavenging activity of 58.71 % and an IC50 value of 67.62, while TSB exhibited a free radical scavenging activity of 57.79 % with an IC50 value of 72. These findings were consistent with molecular docking analysis, suggesting that TSB effectively interacts with the active sites of the target proteins, potentially modulating the inflammatory response. Interestingly, PSB showed superior free radical scavenging activity compared to ASB and TSB, indicating its potential as an effective anti-inflammatory agent.