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 4a—4j were synthesized and screened in silico against...

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Detalles Bibliográficos
Autores principales: Osman, Hasnah, Idris, Nor Hashima, Kamarulzaman, Ezatul Ezleen, Wahab, Habibah A., Hassan, Mohd. Zaheen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518655/
https://www.ncbi.nlm.nih.gov/pubmed/28752033
http://dx.doi.org/10.1016/j.apsb.2017.04.009
Descripción
Sumario: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.

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