4-Thiazolidinone Based 5-Arylidene Hybrids: Design, Synthesis, Antimicrobial Activity, and Molecular Docking Studies

Abstract

In recent years, the most pressing challenge in drug development has been the fight against bacterial drug resistance. Microbes have developed resistance against the present classes of antibiotics, necessitating the development of new antibiotics capable of replacing less effective drugs commercially accessible in the market. In order to achieve this, a straightforward technique for the synthesis of 4-thiazolidinone-based pyrazole-pyridine hybrids was designed (5a–o). The hybrids were characterized using spectroscopic techniques and tested for antimicrobial efficacy against a variety of bacterial and fungal species. The MIC value of compounds 5d, 5f, 5j, 5 l, 5 m, and 5o against tested bacterial strains was 62.5 μg/mL. Compound 5i showed a MIC value of 250 μg/mL against Candida albicans, which is twice the activity of the standard drug. Furthermore, to rationalize the antimicrobial finding and to gain an insight into the plausible mechanism of action, molecular docking study was performed against microbial DNA gyrase. A very significant correlation obtained between the in silico binding affinity and the antimicrobial activity could set an excellent platform for structure based drug design.

Graphical abstract

Keywords:

• 5-Arylidene
• 4-thiazolidinone
• pyridine
• pyrazole
• antimicrobial activity
• molecular docking

Acknowledgments

One of the authors Prof. Nisheeth C. Desai is thankful to UGC for awarding BSR faculty fellowship-2019 (No. F18-1/2011 [BSR]) and financial assistant. Authors are also thankful to Schrödinger Inc. for providing the GLIDE program to perform the molecular docking studies. The authors are thankful to Priyanka Desai, founder of iScribblers for the linguistic editing of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).