| Summary: | 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.
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