title: Computational studies and drug design for HIV-1 reverse transcriptase inhibitors of 3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogs.
abstract: Molecular docking and molecular dynamics simulation were applied to study the binding mode of 3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogs anti-HIV inhibitors with HIV-1 RT. The results suggest that there is a strong hydrogen bond between DCK O16 and NH of Lys101, and that DCK analogues might act similarly as other types of HIV-1 RT inhibitors. The investigation about drug resistance for DCK shows no remarkable influence on the most frequently observed mutation K103N of HIV-1 RT. Based on the proposed mechanism, some new structures were designed and predicted by a SVM model. All compounds exhibited potent inhibitory activities against HIV replication in H9 lymphocytes with EC50 values lower than 1.95 microM. The rationality of the method was validated by experimental results.
authors.affiliation: Department of Chemistry, University Paris 7-Denis Diderot, 1 rue Guy de la Brosse, 75005, Paris, France.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Chen
authors.forename: Bo-Tao
authors.initials: BT
authors.lastname: Fan
authors.forename: Chen-Yang
authors.initials: CY
authors.lastname: Zhao
authors.forename: Lan
authors.initials: L
authors.lastname: Xie
authors.forename: Chun-Hong
authors.initials: CH
authors.lastname: Zhao
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.forename: Graham
authors.initials: G
authors.lastname: Allaway
mesh_terms: D002164:Camphor / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D024882:Drug Resistance, Viral; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C479985:3'R,4'R-di-O-(-)-camphanoyl-(+)-cis-khellactone; D007783:Lactones; D018894:Reverse Transcriptase Inhibitors; D002164:Camphor; D054303:HIV Reverse Transcriptase