3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors.

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 - were synthesized and screened against DENV2 NS2B/NS3 protease to elucidate their binding mechanism and orientation around the active sites. Results were validated through an DENV2 NS2B/NS3 protease assay using a fluorogenic Boc-Gly-Arg-Arg-AMC substrate. Nitro derivatives of 3,5-bis(arylidene)-4-piperidones ( and ) emerged as promising lead molecules for novel protease inhibitors with an IC of 15.22 and 16.23 µmol/L, respectively, compared to the standard, panduratin A, having IC of 57.28 µmol/L.