In Silico Design and Investigation of Novel Thiazetidine Derivatives as Potent Inhibitors of PrpR in Mycobacterium tuberculosis

Abstract

Tuberculosis is one of the most life‐threatening acute infectious diseases diagnosed in humans. In the present investigation, a series of 16 new disubstituted 1,3‐thiazetidines derivatives is designed, and investigated via various in silico methods for their potential as anti‐tubercular agent by evaluating their ability to block the active site of PrpR transcription factor protein of Mycobacterium tuberculosis. The efficacy of the molecules was initially assessed with the help of AutoDock Vina algorithm. Further Glide module is used to redock the previously docked complexes. The binding energies and other physiochemical properties of the designed molecules were evaluated using the Prime‐MM/GBSA and the QikProp module, respectively. The results of docking revealed the nature, site of interaction and the binding affinity between the proposed candidates and the active site of PrpR. Further the inhibitory effect of the scaffolds was predicted and evaluated employing a machine learning‐based algorithm and was used accordingly. Further, the molecular dynamics simulation studies ascertained the binding characteristics of the unique 13, when analysed across a time frame of 100 ns with GROMACS software. The results show that the proposed 1,3‐thiazetidine derivatives such as 10, 11, 13 and 14 could be potent and selective anti‐tubercular agents as compared to the standard drug Pyrazinamide. Finally, this study concludes that designed thiazetidines can be employed as anti‐tubercular agents. Undeniably, the results may guide the experimental biologists to develop safe and non‐toxic drugs against tuberculosis by demanding further in vivo and in vitro analyses.

An in silico approach to investigate the theranostic potential of coumarin‐derived self‐immolative luminescent probes

“…The value of aqueous solubility (QPlogS) should be between −6.5 to 0.5. Table 3 shows the results of ADME analysis [33] . All the proposed molecules are satisfactorily within the above limits and therefore are identified as hit molecules for further analyses.…”

“…Table 3 shows the results of ADME analysis. [33] All the proposed molecules are satisfactorily within the above limits and therefore are identified as hit molecules for further analyses. QPPCaCo is the predicted Caco-2 cell permeability rate.…”

Ionic liquid‐supported copper‐catalyzed synthesis of 2H‐indazoles under microwave irradiation

“…Maintaining our pursuit of investigating the possible uses of bioactive compounds produced via a sustainable route for therapeutic application [56][57][58][59][60][61], herein, we report the ionic liquid-supported copper-catalyzed synthesis of 2H-indazoles under microwaves through the sequential formation of C-N and N-N bonds. The synthetic methods reported in this article include comprehensive details on the formation of the ionic liquid-supported copper catalyst as well as its catalytic application for the preparation of 2H-indazoles.…”

Click-derived multifunctional metal complexes for diverse applications

“…18,21,28 In diagnostic and theranostic research, many luminescent probes have been reported to sense a variety of biological, chemical and environmental analytes but there are still challenges with tuning the luminescence properties of these probes. 29,30 Similarly, the roles of thiazetidines, quinolines and fused imidazoquinolines towards anti-cancer and anti-microbial properties were explored through computational methods, 31,32 but there are limitations in synthesizing these structures; Click chemistry can be employed to overcome these drawbacks. Although some issues exist with the reactivity of Click reactants, efforts to overcome these are underway, particularly for applications like direct conjugation, 19,33 induced drug release and delivery of gaseous signalling molecules.…”