Computational studies and drug design for HIV-1 reverse transcriptase inhibitors of 3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogs.
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.
Chen
Hai-Feng
HF
Department of Chemistry, University Paris 7-Denis Diderot, 1 rue Guy de la Brosse, 75005, Paris, France.
Fan
Bo-Tao
BT
Zhao
Chen-Yang
CY
Xie
Lan
L
Zhao
Chun-Hong
CH
Zhou
Ting
T
Lee
Kuo-Hsiung
KH
Allaway
Graham
G
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*
C479985:3'R,4'R-di-O-(-)-camphanoyl-(+)-cis-khellactone; D007783:Lactones; D018894:Reverse Transcriptase Inhibitors; D002164:Camphor; D054303:HIV Reverse Transcriptase