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


Turkmen Y., YAĞIZ ERDEMİR G., Yuksel Mayda P., AKDEMİR A., GÜNAYDIN AKYILDIZ A., ALTUNDAŞ A.

Journal of Biochemical and Molecular Toxicology, vol.36, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 36
  • Publication Date: 2022
  • Doi Number: 10.1002/jbt.22998
  • Journal Name: Journal of Biochemical and Molecular Toxicology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, Applied Science & Technology Source, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Food Science & Technology Abstracts, MEDLINE
  • Keywords: 1, 2, 3-triazole, 4-(1, 2, 3-triazoyl)arylmethanone, cytotoxicity, heterocycles, M, tuberculosis, CLICK CHEMISTRY, 1,2,3-TRIAZOLES
  • Gazi University Affiliated: Yes

Abstract

© 2022 Wiley Periodicals LLCInfectious 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 (1H, 13C-APT-NMR, FT-IR, and HRMS-TOF). In vitro antimycobacterial activities of the arylmethanone derivatives against the Mycobacterium tuberculosis H37Rv 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.