Journal Article

Structure-based design, synthesis and biological evaluation of β-glucuronidase inhibitors

Zaheer-ul-Haq, Ambreen, Nida, Naureen, Shagufta, Ali, Sajjad, Rasheed, Saima, Choudhary, Mohammad Iqbal, Khan, Khalid M., Halim, Sobia A., Perveen, Shahnaz, Taha, Muhammad

2014

Overview

Using structure-based virtual screening approach, a coumarin derivative ( 1 ) was identified as β-glucuronidase inhibitor. A focused library of coumarin derivatives was synthesized by eco-benign version of chemical reaction, and all synthetic compounds were characterized by using spectroscopy. These compounds were found to be inhibitor of β-glucuronidase with IC 50 values in a micromolar range. All synthetic compounds exhibited interesting inhibitory activity against β-glucuronidase, however, their potency varied substantially from IC 50  = 9.9–352.6 µM. Of twenty-one compounds, four exhibited a better inhibitory profile than the initial hit 1. Interestingly, compounds 1e , 1k , 1n and 1p exhibited more potency than the standard inhibitor with IC 50 values 34.2, 21.4, 11.7, and 9.9 µM, respectively. We further studied their dose responses and also checked our results by using detergent Triton ×-100. We found that our results are true and not affected by detergent.

• Publisher: Springer International Publishing
• Subject: Animal Anatomy / Chemical reactions / Chemistry / Chemistry and Materials Science / Computer aided design / Computer Applications in Chemistry / Coumarin / Crystallography, X-Ray / Derivatives / Detergents / Drug Design / Enzyme Inhibitors - chemical synthesis / Enzyme Inhibitors - chemistry / Enzyme Inhibitors - pharmacology / Glucuronidase - antagonists & inhibitors / Histology / Humans / Inhibitors / Inhibitory Concentration 50 / Models, Molecular / Molecular Structure / Morphology / Physical Chemistry / Triton