Premium
Carbazole‐Linked 1,2,3‐Triazoles: In Vitro β ‐Glucuronidase Inhibitory Potential, Kinetics, and Molecular Docking Studies
Author(s) -
Shaikh Nimra Naveed,
Iqbal Shazia,
Syed Naima,
Khan Maria A.,
Moin Syed Tarique,
Choudhary Muhammad Iqbal,
Basha Fatima Z.
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.201900647
Subject(s) - chemistry , enzyme , in vitro , carbazole , glucuronidase , stereochemistry , dissociation constant , docking (animal) , cell culture , kinetics , biochemistry , microsome , biology , organic chemistry , medicine , physics , nursing , quantum mechanics , receptor , genetics
β‐Glucuronidase enzyme is a tetrameric glycoprotein present in microsomes and lysosomes of many organs, and body fluids. Over‐expression of this enzyme is observed in several melanomas and carcinomas. Therefore, it has been identified as a target for the treatment of several pathological conditions. In this regard, carbazole linked 1,2,3‐triazoles ( 1–27 ) were synthesized according to our previous report, and evaluated for their in vitro β‐glucuronidase inhibitory activities. Compounds 7–10 , 17–18 , 20 , and 22–27 showed potent activities with IC 50 values between 0.55–32.5 μM, as compared to the standard, D‐saccharic acid 1,4‐lactone (IC 50 =45.75 ± 2.16 μM). All active compounds were found to be non‐cytotoxic against mouse fibroblast 3T3 cell line. Compounds 20 , 22 , 23 , 25 , 26 , and 27 were subjected to enzyme kinetic studies for the determination of their modes of inhibition, and dissociation constants Ki. Compounds 23 , 25 , and 26 were also studied for their mode of inhibition by using molecular docking methods.