3D-QSAR and Molecular Docking Studies on Design Anti-Prostate Cancer Curcumin Analogues

Author(s): Xi Meng, Lianhua Cui, Fucheng Song, Mingyuan Luan, Junjie Ji, Hongzong Si*, Yunbo Duan, Honglin Zhai

Journal Name: Current Computer-Aided Drug Design

Volume 16 , Issue 3 , 2020

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Graphical Abstract:


Background: Prostate cancer is one of the most common tumors in the world and the fifth leading cause of male cancer death. Although the treatment of localized androgen-dependent prostate cancer has been successful, the efficacy of androgen-independent metastatic disease is limited. Curcumin, a natural product, has been found to inhibit the proliferation of prostate cancer cells.

Objective: To design curcumin analogs with higher biological activity and lower toxicity and side effects for the treatment of prostate cancer.

Methods: In this study, the three dimensional-quantitative structure activity relationship (3DQSAR) and molecular docking studies were performed on 34 curcumin analogs as anti-prostate cancer compounds. We introduced OSIRIS Property Explorer to predict drug-related properties of newly designed compounds.

Results: The optimum CoMSIA model exhibited statistically significant results: the cross-validated correlation coefficient q2 is 0.540 and non-cross-validated R2 value is 0.984. The external predictive correlation coefficient Rext 2 is 0.792. The information of structure-activity relationship can be obtained from the CoMSIA contour maps. In addition, the molecular docking study of the compounds for 3ZK6 as the protein target revealed important interactions between active compounds and amino acids.

Conclusion: Compound 28i may be a new type of anti-prostate cancer drug with higher biological activity and more promising development.

Keywords: QSAR, CoMSIA, molecular docking, curcumin analogs, drug design, prostate cancer.

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Year: 2020
Page: [245 - 256]
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DOI: 10.2174/1573409914666181029123746
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