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

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.

SUBMITTER: Osman H

PROVIDER: S-EPMC5518655 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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

Osman Hasnah H Idris Nor Hashima NH Kamarulzaman Ezatul Ezleen EE Wahab Habibah A HA Hassan Mohd Zaheen MZ

Acta pharmaceutica Sinica. B 20170504 4

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 as ...[more]

PMID: 28752033

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