Green synthesis, antibacterial and antifungal evaluation of new thiazolidine-2,4-dione derivatives: molecular dynamic simulation, POM study and identification of antitumor pharmacophore sites

Sumeer Ahmed; Ajmal R Bhat; Aziz Kalilur Rahiman; Rajendra S Dongre; Aso Hameed Hasan; Vidya Niranjan; Lavanya C; S A Sheikh; Joazaizulfazli Jamalis; Malika Berredjem; Sarkar M A Kawsar

doi:10.1080/07391102.2023.2258404

Green synthesis, antibacterial and antifungal evaluation of new thiazolidine-2,4-dione derivatives: molecular dynamic simulation, POM study and identification of antitumor pharmacophore sites

J Biomol Struct Dyn. 2023 Sep 28:1-17. doi: 10.1080/07391102.2023.2258404. Online ahead of print.

Authors

Affiliations

¹ Post-Graduate and Research Department of Chemistry, The New College (Autonomous), University of Madras, Chennai, India.
² Department of Chemistry, RTM Nagpur University, Nagpur, India.
³ Department of Chemistry, College of Science, University of Garmian, Kalar, Iraq.
⁴ Department of Biotechnology, R V College of Engineering, Bengaluru, India.
⁵ Department of Physics, National Institute of Technology, Srinagar, Kashmir, India.
⁶ Faculty of Science, Department of Chemistry, Universiti Teknologi Malaysia, Johor, Malaysia.
⁷ Laboratory of Applied Organic Chemistry LCOA, Synthesis of Biomolecules and Molecular Modelling Group, Badji-Mokhtar - Annaba University, Annaba, Algeria.
⁸ Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong, Bangladesh.

PMID: 37768136
DOI: 10.1080/07391102.2023.2258404

Abstract

In this study, a series of thiazolidine-2,4-dione derivatives 3a-i were synthesized and evaluated for antibacterial activity against Gram-positive and Gram-negative strains of Bacillus licheniformis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Newly prepared thiazolidine (TZD) derivatives were further screened separately for in vitro antifungal activity against cultures of fungal species, namely, Aspergillus niger, Alternaria brassicicola, Chaetomium murorum, Fusarium oxysporum, Lycopodium sp. and Penicillium notatum. The electron-donating substituents (-OH and -OCH₃) and electron-withdrawing substituents (-Cl and -NO₂) on the attached arylidene moieties of five-membered heterocyclic ring enhanced the broad spectrum of antimicrobial and antifungal activities. The molecular docking study has revealed that compound 3h strongly interacts with the catalytic residues of the active site of the β-carbonic anhydrase (P. aeruginosa) and has the best docking score. In silico pharmacokinetics studies showed the drug-likeness and non-toxic nature of the synthesized compounds, which indicates the combined antibacterial, antiviral and antitumor pharmacophore sites of the targeted drug. This work demonstrates that potential TZD derivatives bind to different types of bacterial and fungal pathogens for circumventing their activities and opens avenues for the development of newer drug candidates that can target bacterial and fungal pathogens.Communicated by Ramaswamy H. Sarma.

Keywords: antibacterial; antifungal; molecular dynamic simulation; physico-chemical parameters; structure–activity relationship; β-carbonic anhydrase.