Understanding the structure-activity relationship of betulinic acid derivatives as anti-HIV-1 agents by using 3D-QSAR and docking.
Novel anti-HIV-1 agents derived from betulinic acid have been greatly concerned. 3D-QSAR and molecular docking studies were applied to rationalize the structural requirements responsible for the anti-HIV activity of these compounds. The CoMFA and CoMSIA models resulted from 28 molecules gave r(cv)² values of 0.599 and 0.630, r² values of 0.994 and 0.958, respectively. To estimate the predictive ability of the 3D-QSAR model, an external validation was employed. Based on the contour maps generated from both CoMFA and CoMSIA, we have identified some key features in the betulinic acid derivatives that are responsible for the anti-HIV activity. Molecular docking was used to explore the binding mode between these derivatives and HIV gp120. We have therefore designed a series of novel betulinic acid derivatives by utilizing the SAR results revealed in the present study, which were predicted with excellent potencies in the developed models. The results provide a valuable method to design new betulinic acid derivatives as anti-HIV-1 agents.
Lan
Ping
P
Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, People's Republic of China.
Chen
Wan-Na
WN
Huang
Zhi-Jian
ZJ
Sun
Ping-Hua
PH
Chen
Wei-Min
WM
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D015195:Drug Design; D015699:HIV Envelope Protein gp120 / Q000737:chemistry; D015497:HIV-1 / Q000737:chemistry / Q000187:drug effects*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D053978:Pentacyclic Triterpenes; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology; D000094062:Betulinic Acid
D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D000094062:Betulinic Acid