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Quinoline–1,2,3‐triazole Hybrids: Design and Synthesis through Click Reaction, Evaluation of Anti‐Tubercular Activity, Molecular Docking and In Silico ADME Studies
Author(s) -
Reddyrajula Rajkumar,
Dalimba Udayakumar
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201803946
Subject(s) - adme , chemistry , quinoline , triazole , 1,2,3 triazole , docking (animal) , click chemistry , in silico , combinatorial chemistry , stereochemistry , linker , amide , molecule , in vitro , biochemistry , organic chemistry , medicine , nursing , gene , computer science , operating system
A new series of quinoline‐1,2,3‐triazole derivatives ( 6a‐j and 10a‐j ) were designed based on the molecular hybridization concept and the molecules were synthesized by employing a click chemistry approach. The pharmacophoric units (quinoline and 1,2,3‐triazole) are linked through either an ether or an amide functionality; such a simple structural modification of the linker group significantly enhanced the anti‐tubercular activity of the molecules and all the amide derivatives showed better inhibition activity as compared to their ether analogs. However, these compounds did not inhibit significantly the growth of tested bacterial strains: the activity profile is similar to that observed for standard anti‐TB drugs indicating the specificity of these compounds towards the M.tuberculosis strain. The molecular docking studies of the active compounds with two target enzymes (Inh A and CYP121) of M.tuberculosis revealed the strong binding interactions, mainly through hydrogen bonding, between the molecules and the target receptors. Furthermore, prediction of in silico‐ADME (A: absorption, D: distribution, M: metabolism and E: excretion) parameters indicated that these compounds have an excellent oral bioavailability. The results suggest that these quinoline‐1,2,3‐triazole hybrids are a promising class of molecular entities for the development of new anti‐tubercular leads.