Click synthesis of 1,2,3-triazole based imidazoles: Antitubercular evaluation, molecular docking and HSA binding studies

C B Pradeep Kumar; B S Prathibha; K N N Prasad; M S Raghu; M K Prashanth; B K Jayanna; Fahad A Alharthi; S Chandrasekhar; H D Revanasiddappa; K Yogesh Kumar

doi:10.1016/j.bmcl.2021.127810

Click synthesis of 1,2,3-triazole based imidazoles: Antitubercular evaluation, molecular docking and HSA binding studies

Bioorg Med Chem Lett. 2021 Mar 15:36:127810. doi: 10.1016/j.bmcl.2021.127810. Epub 2021 Jan 19.

Authors

Affiliations

¹ Department of Chemistry, Malnad College of Engineering, Hassan 573 202, India.
² Department of Chemistry, B N M Institute of Technology, Bengaluru 560 070, India.
³ Department of Physics, B N M Institute of Technology, Bengaluru 560 070, India.
⁴ Department of Chemistry, New Horizon College of Engineering, Bengaluru 560 103, India.
⁵ Department of Chemistry, B N M Institute of Technology, Bengaluru 560 070, India. Electronic address: prashanthmk87@gmail.com.
⁶ Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
⁷ Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570 006, India.
⁸ Department of Chemistry, School of Engineering and Technology, Jain University, Ramanagara 562 112, India.

PMID: 33482292
DOI: 10.1016/j.bmcl.2021.127810

Abstract

Using Cu(I)-catalyzed cycloaddition of alkyne and azide reaction (CuAAC), a series of novel 1,2,3-triazole based imidazole derivatives (3a-e) have been synthesized. The synthesized molecules were characterized by spectroscopic techniques such as ¹H NMR, ¹³C NMR, mass and elemental analysis. Antitubercular activity (anti-TB) against Mycobacterium tuberculosis H37Rv (Mtb) and cytotoxic activity against the mammalian Vero cell line was screened for the synthesized compounds. The compounds 3d and 3e displayed potent in vitro antitubercular activity and may serve as a lead for further optimization. Besides, the experimental findings were in line with the results of molecular docking. Also, the synthesized compounds have also been analyzed for ADME properties and the experimental finding facilitates the development of new and more potent anti-TB agents in this series in the future. Using fluorescence and UV-vis absorption spectroscopy, the binding interaction of compounds (3d and 3e) with human serum albumin (HSA) was investigated. The results showed that, as a result of HSA-compound complex, the fluorescence quenching of HSA by test compounds was a static quenching process. According to Forster's theory, energy transfer efficiency is calculated.

Keywords: Human serum albumin; Imidazoles; Molecular docking; Triazoles; Tuberculosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antitubercular Agents / chemical synthesis
Antitubercular Agents / chemistry
Antitubercular Agents / pharmacology*
Binding Sites / drug effects
Cell Survival / drug effects
Chlorocebus aethiops
Dose-Response Relationship, Drug
Humans
Imidazoles / chemical synthesis
Imidazoles / chemistry
Imidazoles / pharmacology*
Microbial Sensitivity Tests
Molecular Docking Simulation*
Molecular Structure
Mycobacterium tuberculosis / drug effects*
Serum Albumin, Human / chemistry*
Structure-Activity Relationship
Triazoles / chemistry
Triazoles / pharmacology*
Vero Cells

Substances

Antitubercular Agents
Imidazoles
Triazoles
Serum Albumin, Human