Research on the Anti-tumor Activity of Novel Histone Deacetylase Inhibitors based on 3D QSAR Model

Abstract

Abstract Background Histone deacetylases (HDACs) pertain to the category of Zn2+ or nicotinamide adenine dinucleotide (NAD+)-dependent proteolytic enzymes. While the antitumor effect of HDAC inhibitors alone has been demonstrated and the effect of HDAC inhibitors on solid tumors is not ideal, which considerably limits their clinical use. Therefore, the search for novel HDAC inhibitors equipped with specific inhibitors is extremely urgent and necessary. Methods 3D-QSAR was employed to investigate insights into the crucial structural element that effect the activity of novel HDAC small molecule inhibitors. The best saliency CoMFA and CoMSIA models are obtained using 55 molecules in the training set and 16 molecules in the test set. Results The statistical quality of the generated model is demonstrated by internal and external cross-validations. The CoMFA model obtained satisfactory values (q2 = 0.664, r2 = 0.917, SEE = 0.217) while optimized CoMSIA model exceed with (q2 = 0.672, r2 = 0.948, SEE = 0.175). Conclusion The statistical parameters from 3D-QSAR models reveal that the results are reliable and significant with strong predictive ability. These theoretical results may contribute to the design of novel HDAC small molecule inhibitors with enhanced activity for the treatment of cancer.