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 IC
50
of 15.22 and 16.23 µmol/L, respectively, compared to the standard, panduratin A, having IC
50
of 57.28 µmol/L.
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. Compounds
4e
and
4j
emerged as promising lead molecules for novel protease inhibitors with an IC
50
of 15.22 and 16.23 µmol/L, respectively, compared to the standard, panduratin A, having IC
50
of 57.28 µmol/L.
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