QSAR Study on the Antitumor Activity of Novel 1,2, 3-Triazole Compounds based on Topomer Comfa Method

Background: The high mortality rate of cancer is endangering human health, and the research and development of new anticancer drugs have the attention of scientists worldwide. Sulfonamides have become the focus of anticancer drug research. 1,2,3-triazole compounds can inhibit the formation of a variety of tumor cells. Based on the excellent antitumor activity exhibited by the 1,2,3-triazole compound skeleton, the sulfonamide moiety in the sulfonamide structure can be introduced into the triazole compound skeleton to obtain highly active anticancer drugs. Methods: The Topomer CoMFA method was used to study the three-dimensional quantitative structureactivity relationship of 58 new 1,2,3-triazole compounds with sulfa groups, and a 3D-QSAR model was obtained. Results: The cross-validation coefficient q²is 0.545, the non-cross-correlation coefficient r²is 0. 754, r²predis 0.930, the optimal number of principal components N is 4, and the standard estimation error SEE is 0.319. These results show that the model has good internal and external forecasting capabilities. By searching for the R group in the Topomer search module and combining it with the more active groups in the existing molecules, 6 new compounds with theoretically higher anti-HL-60 (leukemia cell line) activity are obtained. Conclusion: The prediction result of the Topomer CoMFA model is good, and the statistical verification is effective. The prediction results of ADMET show that the 6 new compounds meet the drug requirements and are expected to become potential anti-HL-60 inhibitors, providing guidance for the synthesis of anti-tumor drugs.