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

• Main Authors: Hasnah Osman (Author), Nor Hashima Idris (Author), Ezatul Ezleen Kamarulzaman (Author), Habibah A. Wahab (Author), Mohd. Zaheen Hassan (Author)
• Format: Book
• Published: Elsevier, 2017-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

2211-3835
2211-3843
10.1016/j.apsb.2017.04.009