p-TSA-Promoted Efficient Synthesis of Some New Thiophene Hybridized Thiadiazolyl Schiff Bases as Antibacterial Agents

Abstract

A new series of thiophene hybridized thiadiazolyl Schiff bases was designed and synthesized employing FeCl3-mediated cyclization of thiosemicarbazoneinto thiadiazoles and their subsequent Schiff bases formation using p-TSA in benzene. To understand the interaction of the proposed compounds with β-lactamase (Protein Data Bank [PDB] ID: 3UDI), a molecular docking was performed. All the compounds demonstrated an optimal binding affinity with β-lactamase (−8.17 to −9.75 kcal/mol) and showed crucial hydrogen bonds and π–π interaction with the leading amino acids Arg298, Ala300, and Val391 located at the active site of β-lactamase. The in vitro antibacterial activity of the desired molecules was conducted against few gram-positive and Gram-negative bacterial strains using amoxicillinas reference drug. The compound having p-hydroxyphenyl substituent (3c) was found to be potentially effective to inhibit P. aeruginosa and E. coli with MIC value 7.5 μg/mL and 9.0 μg/mL, respectively, whereas other compounds exhibited moderate to good activity. Altogether, the primary in-vitro screening of newly synthesized thiophene hybridized thiadiazole Schiff bases opens a new venture towards the development of promising alternatives of β-lactamase inhibitors as anti-bacterial agents.