Synthesis, anti‐TB activities, and molecular docking studies of 4‐(1,2,3‐triazoyl)arylmethanone derivatives

Abstract

Infectious diseases such as tuberculosis (TB) are leading causes of human death.Antibiotics are effective molecules to combat bacterial infections by affecting the processes required for bacterial cell growth and proliferation. The development of new antibiotics has become an important issue as overdosed or incorrect use of antibiotic lead to the development of antibiotic resistance. In this study, a new series of 4-(1,2,3-triazoyl)arylmethanone derivatives has been synthesized using the one-pot Copper-Catalyzed Oxidative Cross-Dehydrogenative Coupling/Oxidative Cycloaddition strategy to overcome the aforementioned problems. New compounds were characterized by using spectroscopic techniques ( 1 H, 13 C-APT-NMR, FT-IR, and HRMS-TOF). In vitro antimycobacterial activities of the arylmethanone derivatives against the Mycobacterium tuberculosis H 37 Rv standard strain were examined using the resazurin microplate method in the presence of streptomycin and rifampycin as standard medicines. Bioactive assays demonstrated promising results that some of the synthesized 4-(1,2,3-triazoyl) arylmethanone derivatives exhibited good anti-TB activities. Notably, compounds 6b, 6f, and 6g gave the most potent efficiency with minimum inhibitory concentration values of 4 μg/ml (12.8, 11.7, and 12.8 μΜ, respectively). Among the synthesized compounds, the cytotoxicity measurements of the 6b, 6f, 6g, 6d, and 6v derivatives were screened and it was found that the 6f derivative did not show any cytotoxicity. Molecular docking analyses are utilized to identify the binding mode and the key interactions between target compounds and the ligand-binding site of M. tuberculosis enoyl-acyl carrier protein reductase enzyme (MtInhA, EC 1.3.1.9). The docking results were in agreement with the in vitro results, which confirm the synthesized ligands bind to MtInha with moderate to low affinity.

Computational drug repurposing effort for identifying novel hits for the treatment of diseases such as endometriosis, uterine fibroids, and prostate cancer

“…The literature supported these residues, and residues that should interact with an antagonist ligand were determined [ 48 , 50 – 52 ]. In addition, high affinity for the binding site was evaluated between ligands docking to the receptor structure [ 29 , 52 , 54 ].…”

Dermato-cosmeceutical properties of Pseudobombax ellipticum (Kunth) Dugand: Chemical profiling, in vitro and in silico studies

“…It is very important to monitor how the obtained numerical data changes during the molecular dynamics simulation in order to view how the stability of the complexes changes over time. The MM-GBSA calculation was used to estimate the binding free energy of the complexes ( Turkmen et al, 2022 ). MM-GBSA calculation was made once every 400 frames.…”

Synthesis of 1,4-disubstituted-1,2,3-Triazole derivatives for investigation of inhibition and molecular docking studies against Xanthine Oxidase

“…22,23 It is seen that among the 1,2,3-triazoles derivatives, especially the derivatives at the 4-position on this ring have attention due to strong interactions with enzymes in the recent studies. 24,25 Recently, it is indicated that these compounds containing the azole ring have a better XO inhibitory effect than allopurinol. [26][27][28]…”