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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Main Authors: Osman, Hasnah, Idris, Nor Hashima, Kamarulzaman, Ezatul Ezleen, A. Wahab, Habibah, Hassan, Mohd. Zaheen
Format: Article
Published: Elsevier 2017
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Online Access:http://eprints.usm.my/37959/
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author Osman, Hasnah
Idris, Nor Hashima
Kamarulzaman, Ezatul Ezleen
A. Wahab, Habibah
Hassan, Mohd. Zaheen
author_facet Osman, Hasnah
Idris, Nor Hashima
Kamarulzaman, Ezatul Ezleen
A. Wahab, Habibah
Hassan, Mohd. Zaheen
author_sort Osman, Hasnah
building USM Institutional Repository
collection Online Access
description 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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spelling usm-379592017-12-19T01:58:00Z http://eprints.usm.my/37959/ 3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors Osman, Hasnah Idris, Nor Hashima Kamarulzaman, Ezatul Ezleen A. Wahab, Habibah Hassan, Mohd. Zaheen QD1-999 Chemistry RS1-441 Pharmacy and materia medica 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. Elsevier 2017-07 Article PeerReviewed Osman, Hasnah and Idris, Nor Hashima and Kamarulzaman, Ezatul Ezleen and A. Wahab, Habibah and Hassan, Mohd. Zaheen (2017) 3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors. Acta Pharmaceutica Sinica B, 7 (4). pp. 479-484. ISSN 2211-3835 http://dx.doi.org/10.1016/j.apsb.2017.04.009
spellingShingle QD1-999 Chemistry
RS1-441 Pharmacy and materia medica
Osman, Hasnah
Idris, Nor Hashima
Kamarulzaman, Ezatul Ezleen
A. Wahab, Habibah
Hassan, Mohd. Zaheen
3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors
title 3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors
title_full 3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors
title_fullStr 3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors
title_full_unstemmed 3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors
title_short 3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors
title_sort 3,5-bis(arylidene)-4-piperidones as potential dengue protease inhibitors
topic QD1-999 Chemistry
RS1-441 Pharmacy and materia medica
url http://eprints.usm.my/37959/
http://eprints.usm.my/37959/