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

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
• physico-chemical parameters
• molecular dynamic simulation
• structure–activity relationship
• β-carbonic anhydrase

Acknowledgements

We gratefully acknowledges the Council of Scientific and Industrial Research (CSIR), New Delhi, India, for providing financial assistance in the form of Senior Research Fellowship (SRF, File No.: 08/743(001)/2020-EMR-I).

Author contributions

Sumeer Ahmed—molecular docking study and writing, Aziz Kalilur Rahiman—resources and supervision, Ajmal R. Bhat—POM analysis, experimental work and biological studies, Rajendra S. Dongre—formal analysis and investigations, Vidya Niranjan and Lavanya C—molecular dynamic simulations, S. A. Sheikh—validation and visualization. Aso Hameed Hasan and Joazaizulfazli Jamalis—review and editing, Malika Berredjem and Sarkar M.A. Kawsar—computational analysis and methodology. All the authors read and approved the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.