Discovery of novel arylethynyltriazole ribonucleosides with selective and effective antiviral and antiproliferative activity.
Novel ethynyltriazole ribonucleosides were synthesized using a simple and efficient two-step procedure involving Sonogashira coupling and subsequent ammonolysis. Compounds 2f and 3o inhibited hepatitis C virus (HCV) replication efficiently, whereas compound 3f demonstrated potent apoptosis-induced antiproliferative activity against pancreatic cancer MiaPaCa-2 cells both in vitro and in vivo. Most interestingly, the notable selective antiviral and antiproliferative activities were achieved respectively for 2f and 3f by modulating the ribose sugar moiety into deprotected and protected forms while retaining a similar trifluoromethylphenylethynyltriazole as the nucleobase. Preliminary structure-activity relationship study revealed that not only the ribose moiety but also the CF(3) group at the p-position of the phenyl ring and the rigid triple bond functionality contributed critically to the observed antiviral activity of 2f against HCV and antiproliferative activity of 3f against pancreatic cancer. These two compounds constitute therefore promising leads in the search for new antiviral and anticancer candidates.
Wan
Jinqiao
J
State Key Laboratory of Virology, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, PR China.
Xia
Yi
Y
Liu
Yang
Y
Wang
Menghua
M
Rocchi
Palma
P
Yao
Jianhua
J
Qu
Fanqi
F
Neyts
Johan
J
Iovanna
Juan L
JL
Peng
Ling
L
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000187:drug effects; D006801:Humans; D008968:Molecular Conformation / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D012263:Ribonucleosides / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D012263:Ribonucleosides; D014230:Triazoles