title: Highly suppressing wild-type HIV-1 and Y181C mutant HIV-1 strains by 10-chloromethyl-11-demethyl-12-oxo-calanolide A with druggable profile.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hai
authors.initials: H
authors.lastname: Xue
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Lu
authors.forename: Purong
authors.initials: P
authors.lastname: Zheng
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Chunyan
authors.initials: C
authors.lastname: Han
authors.forename: Jinping
authors.initials: J
authors.lastname: Hu
authors.forename: Zijie
authors.initials: Z
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Ma
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Chen
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: 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
chemical_list: C547679:10-chloromethyl-11-demethyl-12-oxocalanolide A; D019380:Anti-HIV Agents; D039681:Pyranocoumarins