Affiliations 

  • 1 School of Chemical Sciences, Universiti Sains Malaysia, Pulau Pinang 11800 USM, Malaysia
  • 2 School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Pinang 11800 USM, Malaysia
Acta Pharm Sin B, 2017 Jul;7(4):479-484.
PMID: 28752033 DOI: 10.1016/j.apsb.2017.04.009

Abstract

Dengue is a severe mosquito-borne viral infection causing half a million deaths annually. Dengue virus NS2B/NS3 protease is a validated target for anti-dengue drug design. A series of hitherto unreported 3,5-bis(arylidene)-4-piperidones analogues 4a-4j were synthesized and screened in silico against DENV2 NS2B/NS3 protease to elucidate their binding mechanism and orientation around the active sites. Results were validated through an in vitro DENV2 NS2B/NS3 protease assay using a fluorogenic Boc-Gly-Arg-Arg-AMC substrate. Nitro derivatives of 3,5-bis(arylidene)-4-piperidones (4e and 4j) emerged as promising lead molecules for novel protease inhibitors with an IC50 of 15.22 and 16.23 µmol/L, respectively, compared to the standard, panduratin A, having IC50 of 57.28 µmol/L.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.