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

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

Dengue is a severe mosquito-borne viral in fection causing half a million deaths annually. Dengue virusNS2B/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...

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Bibliographic Details
Main Authors: Osman, Hasnah, Idris, Nor Hashima, Kamarulzaman, Ezatul Ezleen, A. Wahab, Habibah, Hassan, Mohd. Zaheen
Format: Article
Published: Elsevier 2017
Subjects:
QD1-999 Chemistry
RS1-441 Pharmacy and materia medica
Online Access:http://eprints.usm.my/37959/
Description
Summary:Dengue is a severe mosquito-borne viral in fection causing half a million deaths annually. Dengue virusNS2B/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-is(arylidene)-4-piperidones(4e and 4j) merged as promising lead molecules for novel protease inhibitors with an IC50 of 15.22 and 16.23 umoI/L, respectively, compared to the standard, panduratin A, having IC50 of 57.28 umoI/L.

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