Mechanism-based structure-activity relationship (SAR) analysis of aromatic amines and nitroaromatics carcinogenicity via statistical analyses based on CPDB

Abstract

Cancer is a leading cause of human mortality around the globe. In this study, mechanism-based SAR (Structure-Activity Relationship) was employed to investigate the carcinogenicity of aromatic amines and nitroaromatics based on CPDB. Principal component analysis and cluster analysis were used to construct the SAR model. Principle component analysis generated three principal components from 12 mechanism-based descriptors. The extracted principal components were later used for cluster analysis, which divided the selected 55 chemicals into six clusters. The three principal components were proposed to describe the "transport", "reactivity" and "electrophilicity" properties of the chemicals. Cluster analysis indicated that the relevant "transport" properties positively correlated with the carcinogenic potential and were contributing factors in determining the carcinogenicity of the studied chemicals. The mechanism-based SAR analysis suggested the electron donating groups, electron withdrawing groups and planarity are significant factors in determining the carcinogenic potency for studied aromatic compounds. The present study may provide insights into the relationship between the three proposed properties and the carcinogenesis of aromatic amines and nitroaromatics.

Keywords: Aromatic amine; Carcinogenicity; Cluster analysis; Mechanism-based SAR; Nitroaromatics; Principal component analysis.