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

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

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 values in a micromolar range. All synthetic compounds exhibited interesting inhibitory activity against β-glucuronidase, however, their potency varied substantially from IC = 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 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.

GLYCOSIDASES; GLUCURONIDASE; CLEANING compounds; ANTICOAGULANTS; CHEMICAL processes; CHEMICAL reactions

Journal of Computer-Aided Molecular Design, 2014, Vol 28, Issue 5, p577

0920-654X

Academic Journal

10.1007/s10822-014-9745-z