Journal of Medicinal Chemistry p. 2333 - 2347 (2019)
Update date:2022-08-15
Topics:
Brai, Annalaura
Martelli, Francesco
Riva, Valentina
Garbelli, Anna
Fazi, Roberta
Zamperini, Claudio
Pollutri, Alessandro
Falsitta, Lucia
Ronzini, Stefania
Maccari, Laura
Maga, Giovanni
Giannecchini, Simone
Botta, Maurizio
Increased frequency of arbovirus outbreaks in the last 10 years represents an important emergence for global health. Climate warming, extensive urbanization of tropical regions, and human migration flows facilitate the expansion of anthropophilic mosquitos and the emerging or re-emerging of new viral infections. Only recently the human adenosinetriphosphatase/RNA helicase X-linked DEAD-box polypeptide 3 (DDX3X) emerged as a novel therapeutic target in the fight against infectious diseases. Herein, starting from our previous studies, a new family of DDX3X inhibitors was designed, synthesized, validated on the target enzyme, and evaluated against the West Nile virus (WNV) infection. Time of addition experiments after virus infection indicated that the compounds exerted their antiviral activities after the entry process, likely at the protein translation step of WNV replication. Finally, the most interesting compounds were then analyzed for their in vitro pharmacokinetic parameters, revealing favorable absorption, distribution, metabolism, and excretion values. The good safety profile together with a good activity against WNV for which no treatments are currently available, make this new class of molecules a good starting point for further in vivo studies.
View Morewebsite:http://www.antimex.com
Contact:0086-21-50563169
Address:Room1027,No.Jinyu Road,Pudong
Contact:+86-0512-62857507
Address:Boji Science Park, No1688C,Taishan road, Suzhou ,China
ZhangJiaGang YaRui Chemical Co.,Ltd.
Contact:0512-58360968
Address:China JiangSu Province Zhang Jia Gang City YangShe Oriental Plaza Building 10 B307
HANGZHOU PANYU CHEMICAL CO.,LIMITED
Contact:+86-571-86578491
Address:Rm 605, NO.1870 Binsheng Road,Binjiang Dist, Hangzhou, China
Shanghai AoBo Bio-Pharmaceutical Technology Co., Ltd.
Contact:+86-21-51320130-801, 816
Address:Room 601, No. 1011, Halei Road, Zhangjiang High-Tech Park, Pudong, Shanghai
Doi:10.1016/j.poly.2018.12.007
(2019)Doi:10.1039/c39920000411
(1992)Doi:10.1134/S1070363212100143
(2012)Doi:10.1039/c7ra08086g
(2017)Doi:10.1016/j.tet.2017.03.028
(2017)Doi:10.1248/cpb.40.518
(1992)