ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Substituted isatin-thiosemicarbazones containing d-galactose moiety: Synthesis, antimicrobial inhibition assay and molecular simulation study

Nguyen Dinh Thanh, Nguyen Thi Kim Giang, Vu Ngoc Toan, Hoang Thi Kim Van, Do Son Hai, Nguyen Minh Tri, and Duong Ngoc Toan

Faculty of Chemistry, VNU University of Science (Vietnam Nation University), Hanoi, Vietnam

E-mail: nguyendinhthanh@hus.edu.vn

Received: 20 May 2023  Accepted: 12 September 2023

Abstract:

Thiosemicarbazone scaffolds had multifaceted reactivity as well as exhibit a remarkable range of biological activity, such as anti-oxidant, antibacterial, anticancer, and antifungal activity. In this work, some new substituted galactose-conjugated isatin-thiosemicarbazones 4a–4h had been synthesized and studied for their antibacterial and antifungal activity. Some compounds had the strong inhibitory activity against several S. aureus enzymes, including two enzymes of bacterial topoisomerase type II, DNA gyrase and DNA topoisomerase IV (Topo IV). The obtained results showed that three potential derivatives, including 5-chloroisatin (4c), 5-bromoisatin (4d), and 5,7-dibromoisatin (4d) N-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)thiosemicarbazones, exhibited remarkable activity on antimicrobial tests for five Gram-(+) and four Gram-(−) bacterial strains as well as five fungal strains. These most potent compounds were further studied induced fit docking and MM-GBSA researches. The obtained results indicated that H-binding interactions with residue Arg1122 on chain B as well as stacking π–π interactions with residues DG10 and DC11 on chain E were important interactions. These interactions perhaps determined the high bioactivity of compound 4c. The 280 ns-MD simulation showed all the dynamic interactions that took place between inhibitor 4c and residues in active pocket of enzyme S. aureus 2XCS when this inhibitor entered and settled in this pocket. It was located stably in the receptor and caused the necessary biological reaction.

Keywords: Isatin; Antibacterial; Antifungal; d-Galactose; Sugar thiosemicarbazide; Thiosemicarbazones; Molecular simulations

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-023-03083-w

Chemical Papers 77 (12) 7813–7834 (2023)