Click chemistry enabled synthesis of quinolin-3-yl based 1,2,3-triazoles and in silico screening

A new series of quinoline-based 1,4-disubstituted 1,2,3-triazole derivatives was designed and synthesized using 2-chloroquinoline-3-carbaldehyde as a key precursor. The target molecules were successfully synthesized through copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) by coupling terminal alkynes with various aryl azides, which are generated through diazotization of corresponding anilines. All synthesized compounds were comprehensively characterized using appropriate spectroscopic techniques such as FTIR, 1H NMR, 13C NMR, DEPT-135, and HRMS. Single crystal X-ray diffraction (SC-XRD) analysis of compound 9b confirmed its molecular structure and revealed a triclinic crystal lattice system with the space group P1. The photophysical properties of the synthesized derivatives were studied through UV–visible absorption and fluorescence emission spectroscopy. In addition, Density functional theory (DFT) calculations were performed to optimize molecular geometries and to elucidate their electronic properties using frontier molecular orbital (HOMO–LUMO) analysis and molecular electrostatic potential (MEP) mapping. Molecular docking studies against the Mycobacterium tuberculosis target enzyme lanosterol 14α-demethylase (CYP51; PDB ID: 1E9X) revealed strong theoretical binding affinities for several derivatives, with compounds 9a (− 10.85 kcal/mol) and 9g (− 10.31 kcal/mol) exhibiting the most favorable interactions, along with low predicted inhibition constants.