Highly suppressing wild-type HIV-1 and Y181C mutant HIV-1 strains by 10-chloromethyl-11-demethyl-12-oxo-calanolide A with druggable profile.
We herein report a new compound: 10-chloromethyl-11-demethyl-12-oxo-calanolide A (20, EC(50) = 7.4 nM, SI = 1417), which demonstrates a druggable profile with 32.7% oral bioavailability in rat, tolerated oral single dose toxicity in mice, and especially the feature of highly efficient suppression of the wild-type HIV-1 and Y181C mutant HIV-1 at an EC(50) = 7.4 nM and EC(50) = 0.46 nM, respectively.
Xue
Hai
H
Department of Synthetic Medicinal Chemistry, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 2 Nan Wei Road, Beijing 100050, China.
Lu
Xiaofan
X
Zheng
Purong
P
Liu
Li
L
Han
Chunyan
C
Hu
Jinping
J
Liu
Zijie
Z
Ma
Tao
T
Li
Yan
Y
Wang
Lin
L
Chen
Zhiwei
Z
Liu
Gang
G
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001682:Biological Availability; D001921:Brain / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D020128:Inhibitory Concentration 50; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation / Q000235:genetics; D039681:Pyranocoumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
C547679:10-chloromethyl-11-demethyl-12-oxocalanolide A; D019380:Anti-HIV Agents; D039681:Pyranocoumarins