S-alkylated thiosemicarbazone derivatives: Synthesis, crystal structure determination, antimicrobial activity evaluation and molecular docking studies

Abstract

Increasing antimicrobial resistance is one of the most serious threats to human health worldwide. Therefore, there is an urgent need for the discovery of novel antimicrobial agents. Herein, we presented the synthesis of ten thiosemicarbazone derivatives (T1-T10) obtained by the reaction of S-alkylthiosemicarbazide with various dicarbonyl derivatives. The compounds were characterized by IR, H-1 NMR, ESI-MS and X-ray crystallography. Reaction with the dicarbonyl compound bearing the 4-fluorobenzoyl group unexpectedly gave a pyrazole derivative (T8) containing the entire S-methylthiosemicarbazone backbone. We extensively screened these derivatives for their antimicrobial activities against Mycobacterium tuberculosis and various bacterial and Candida strains. Additionally, the biofilm inhibition capacity of T8 was evaluated on Staphylococcus epidermidis and Pseudomonas aeruginosa biofilm positive strains. To find out the potential mechanism of anti-biofilm activity against PAO1, the docking studies of T8 were carried out into the binding site of LasR, which is the main regulator of bacterial cell-to-cell communication system known as quorum sensing. (C) 2021 Elsevier B.V. All rights reserved.