Antitubercular activity assessment of fluorinated chalcones, 2-aminopyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives: In vitro, molecular docking and in-silico drug likeliness studies

Abstract

A series of newer previously synthesized fluorinated chalcones and their 2-amino-pyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives were screened for their in vitro antitubercular activity and in silico methods. Compound 40 (MIC~ 8 μM) was the most potent among all 60 compounds, whose potency is comparable with broad spectrum antibiotics like ciprofloxacin and streptomycin and three times more potent than pyrazinamide. Additionally, compound 40 was also less selective and hence non-toxic towards the human live cell lines-LO2 in its MTT assay. Compounds 30, 27, 50, 41, 51, and 60 have exhibited streptomycin like activity (MIC~16–18 μM). Fluorinated chalcones, pyridine and pyran derivatives were found to occupy prime position in thymidylate kinase enzymatic pockets in molecular docking studies. The molecule 40 being most potent had shown a binding energy of -9.67 Kcal/mol, while docking against thymidylate kinase, which was compared with its in vitro MIC value (~8 μM). These findings suggest that 2-aminopyridine-3-carbonitrile and 2-amino-4H-pyran-3-carbonitrile derivatives are prospective lead molecules for the development of novel antitubercular drugs.

New bis-heterocyclic structures: Synthesis, characterization and biological activity

“…The biological activity of the compounds prepared was investigated by their effect on three bacteria Escherichia coli, Klebsiella pneumonia and Staphylococcus aureus by diffusion in an agar medium and nutrient. 22 The compounds prepared showed a significant, clear and selective effect against the Staphylococci when compared to the results found for the other bacteria. 23 From these results, Compound 1 showed an inhibitory effect with its best effect at a concentration of 150 mg/mL.…”

Design, synthesis, biological and computational screening of novel pyridine-based thiadiazole derivatives as prospective anti-inflammatory agents

“…Molecular Docking and simulation studies were performed using Chemoffice 2016 tools, Discovery Studio 2020 software, AutodocVina module of PyRx 0.8 software [ [64] , [65] , [66] ], a DELL workstation running the 64-bit Ubuntu 22.04 LTS operating system, an Intel Core i5-12400 processor clocked at 2.30 GHz, 16 GB of RAM, and an 8 GB Nvidia GeForce RTX 3050 GPU, Desmond module of the Schrodinger Suite, (created by the D.E. Shaw research team and used under an academic license) [ 67 ].…”

Comprehensive Study of Chalcone Derivatives

“…Based on the strong binding-affinity scores obtained during molecular docking experiments against the receptors, MTB phosphotyrosinephosphatase B protein was identified as the most likely target. [24] Babu et al [25] investigated the antitubercular activity of chalcones containing nitrophenyl moieties using the MABA assay as well as the antibacterial and antifungal activities using the cup plate technique. A molecular docking study anticipated that Mycobacterium tuberculosis thymi-dine kinase would be inhibited.…”