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
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 2
Rext 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.