3,5-Bis(arylidene)-4-piperidonesaspotential dengue proteaseinhibitors

• Main Authors: Osman, Hasnah, Idris, Nor Hashima, Kamarulzaman, Ezatul Ezleen, A.Wahab, Habibah, Hassan, Mohd. Zaheen
• Format: Article
• Published: Elsevier 2017
• Subjects: RS1-441 Pharmacy and materia medica
• Online Access: http://eprints.usm.my/36660/; http://dx.doi.org/10.1016/j.apsb.2017.04.009

Dengue isaseveremosquito-borneviralinfectioncausinghalfamilliondeathsannually. Dengue virusNS2B/NS3proteaseisavalidatedtargetforanti-denguedrugdesign.Aseriesofhitherto unreported 3,5-bis(arylidene)-4-piperidonesanalogues 4a–4j were synthesizedandscreened in silico against DENV2NS2B/NS3proteasetoelucidatetheirbindingmechanismandorientationaroundthe active sites.Resultswerevalidatedthroughan in vitro DENV2 NS2B/NS3proteaseassayusinga fluorogenic Boc-Gly-Arg-Arg-AMCsubstrate.Nitroderivativesof3,5-bis(arylidene)-4-piperidones(4e and 4j) emergedaspromisingleadmoleculesfornovelproteaseinhibitorswithanIC50 of 15.22and 16.23 mmol/L, respectively,comparedtothestandard,panduratinA,havingIC50 of 57.28 mmol/L.