Quantitative structure-activity relationships study of a series of niacinamide analogues as androgen receptor antagonists

Prostate cancer (PCa) is one of the most common male cancers worldwidely. The androgen receptor (AR) antagonists are clinically prescribed to treat prostate cancer. Patients have shown various degrees of resistance to marketed AR antagonists, which drives the need for the development of new androgen receptor antagonist. Recently, a series of nicotinamide derivatives have been reported as novel AR antagonists. In this study, 3D Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) were employed to construct quantitative structure-activity relationship (QSAR) models of a series of niacinamide analogues as antiandrogens. The obtained models have good reliability and predictivity. In addition, the contour maps from the models can intuitively aid to understand the vital structural characteristics of niacinamides related with the AR antagonistic activities. Our study provides important guidance for the rational design and screening of highly potential active antiandrogens. •CoMFA and CoMSIA QSAR models with good reliability and predictivity were obtained on a series of Niacinamide analogues as antiandrogens.•The contour plots show the core groups that are closely related to the activity.•The detailed relationships between structures and bioactivities were summarized in a figure to facilitate the optimization of these antiandogens.