Understanding the structure-activity relationship of betulinic acid derivatives as anti-HIV-1 agents by using 3D-QSAR and docking |
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Authors: | Ping Lan Wan-Na Chen Zhi-Jian Huang Ping-Hua Sun Wei-Min Chen |
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Institution: | (1) 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; |
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Abstract: | 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
cv2 values of 0.599 and 0.630, r
2
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. |
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Keywords: | |
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