Synthesis, In silico and Biological Studies of Thiazolyl-2h-chromen-2-one Derivatives as Potent Antitubercular Agents

Abstract

Background: A series of new six thiazolyl-2-amine based Schiff base derivatives (4a-4f) were synthesized by a sequential multistep reactions starting with Salicylaldehyde. Objective: All the Schiff base derivatives were screened in-vitro for their antibacterial activity against Mycobacterium tuberculosis (H37RV strain) ATCC No-27294. The synthesized compounds were characterized by FTIR, 1H-NMR, 13C-NMR and Mass spectrometry. Results: Among the compounds tested, 4c and 4f exhibited potent antitubercular activity against M. Tuberculosis at MIC 6.25 µg/mL. Conclusion: We extended our study to explore the inhibition mechanism by conducting molecular docking analysis by using Schrodinger’s molecular modeling software. All the newly synthesized compounds were found to be in-silico AMES test non-toxic and non-carcinogens. The good Qikprop’s Absorption, Distribution, Metabolism and Excretion (ADMET) would definitely be help the researchers in order to make more potent Anti-TB agents.

Ethionamide and Prothionamide Based Coumarinyl-Thiazole Derivatives: Synthesis, Antitubercular Activity, Toxicity Investigations and Molecular Docking Studies

“…The literature has reported molecules similar to 4a-4j (compounds A and B of Fig. 1 ) [ 6 , 7 ]. Compound A of Fig.…”

“…Coumarinthiazole based compounds (Fig. 1 ) have also been reported as potent anti-TB agents [ 6 , 7 ]. Ethionamide (ETH) and prothioanamide (PTH) are thioamide groups containing second-line anti-TB drugs, which are utilized as a replacement for INH and rifampin in the case of MDR-TB.…”

“…This leads to an increase in the treatment duration (up to two years) and the probability of increased side effects [ 8 ]. The literature teaches that the thioamide group of ETH and PTH can cyclize to thiazole derivatives after reaction with phenyl acyl bromide, for example, with 3-coumarinylacetyl bromide [ 6 , 7 , 9 ]. Therefore, in continuation of our endeavor to develop anti-TB compounds [ 10 , 11 ] and because of the challenges associated with TB [ 1 , 2 ], the author decided to develop ETH and PTH-based coumarinylthiazole derivatives as anti-TB agents.…”

“…1. Design of the compounds A and B: The structure of coumarin-thiazole based compounds as anti-TB agents reported in reference [ 6 , 7 ], respectively. 4a-4j: The structure of the synthesized compounds as anti-TB agents.…”

Greener Synthesis, In-Silico and Theoretical Analysis of Hydrazides as Potential Antituberculosis Agents (Part 1)

“…Antimicrobial resistance is a severe global healthcare threat, which is hampering the quality of human life [1][2][3][4]. Searching for potent, safe, and effective agents is still a difficult task for medicinal chemists all over the world.…”