title: Structural modifications of 5,6-dihydroxypyrimidines with anti-HIV activity.
abstract: A series of 5,6-dihydroxypyrimidine analogs were synthesized and evaluated for their anti-HIV activity in vitro. Among all of the analogs, several compounds exhibited significant anti-HIV activity, especially 1b and 1e, which showed the most potent anti-HIV activity with EC(50) values of 0.14 and 0.15 μM, and TI (therapeutic index) values of >300 and >900, respectively. Further docking studies revealed that the representative compounds 1e and 3a could meet the HIV-1 integrase inhibition minimal requirements of a chelating domain (two metal ions) and an aromatic domain (π-π stacking interactions).
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, PR China.
authors.forename: Di-Liang
authors.initials: DL
authors.lastname: Guo
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Zhang
authors.forename: Rui-Rui
authors.initials: RR
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Zeng
authors.initials: Z
authors.lastname: Li
authors.forename: Jin-Yi
authors.initials: JY
authors.lastname: Xu
authors.forename: Kai-Xian
authors.initials: KX
authors.lastname: Chen
authors.forename: Yong-Tang
authors.initials: YT
authors.lastname: Zheng
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D019428:HIV Integrase Inhibitors; D011743:Pyrimidines; D019427:HIV Integrase; C030986:pyrimidine; C514801:p31 integrase protein, Human immunodeficiency virus 1