Design and synthesis of new 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one analogs as Mycobacterium tuberculosis DNA gyrase inhibitors

Preeti S Salve,Shankar G Alegaon,Sunil S Jalalpure,Prajakta Parchure,Rohini S Kavalapure,Lisel Araujo,Madhu Rekha Estharla,Vagolu Siva Krishna,Dharmarajan Sriram

doi:10.1186/s43094-020-00162-7

Abstract

BackgroundTuberculosis is evidently a major health threat among human populations worldwide. The current study presents the synthesis of new 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one analogs (4a–o) as potential Mycobacterium tuberculosis DNA gyrase inhibitors. DNA gyrase regulates DNA topology in MTB and has been a target of choice for antibacterial therapy. With this in mind, the synthesized derivatives (4a–o) were subjected to in vitro antitubercular evaluation by the MABA method and were tested for MTB DNA gyrase inhibition by supercoiling assay.ResultsAll the synthesized compounds displayed inhibition of MTB within the MIC range of 1.56–12.5 μM. Further, out of the selected compounds that underwent DNA gyrase inhibition, compound 4o proved to be a potent lead molecule by displaying 82% of enzyme inhibition at 1 μM. All the synthesized derivatives also underwent molecular docking studies to comprehend their hypothetical binding interactions with Mycobacterium smegmatis GyrB.ConclusionAll the results suggested that most of the synthesized derivatives inhibited Mycobacterium tuberculosis, and some 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one analogs could act as leads for the development of antitubercular agents.

Highlights

Tuberculosis is a major health threat among human populations worldwide
TB is primarily caused by Mycobacterium tuberculosis (MTB) and has been one of the prime killers among communicable diseases caused by a sole infectious agent in humans, in their most productive age of 15–49 years
All the synthesized derivatives underwent proton Nuclear magnetic resonance (NMR) spectral studies. It was evident from the NMR spectra that a singlet signal appeared around 2.72 ppm, which was attributed to the CH proton at the C-2 position in the thiazolidinyl ring

Summary

Introduction

Tuberculosis is a major health threat among human populations worldwide. DNA gyrase regulates DNA topology in MTB and has been a target of choice for antibacterial therapy. Tuberculosis (TB) has single-handedly been successful in causing major health threats among human populations worldwide. TB is primarily caused by Mycobacterium tuberculosis (MTB) and has been one of the prime killers among communicable diseases caused by a sole infectious agent in humans, in their most productive age of 15–49 years. This lethal disease has been steadily devouring millions of individuals every year causing ill health and death throughout the globe. The Indian and the global scenario of the devastating ailment of TB has reached an alarming stage and needs to be efficiently curbed in order to ensure a better quality of life for all human mankind

Methods

Results

Discussion

Conclusion