Design, synthesis, and high-throughput in vitro anti-cancer evaluation of novel 4-aminopyrazolo[3,4-d]pyrimidine derivatives: potential anti-cancer candidates against UO-31 renal cancer cells

Abstract

A novel series of 20 compounds containing 4-aminopyrazolo[3,4-d]pyrimidine core were synthesized, characterized and their chemical structures confirmed using spectroscopic techniques such as ¹H NMR, ¹³C NMR, IR, and HRMS. The compound's growth inhibitory activities were evaluated against 60 human tumor cell lines from nine panels: leukemia, non-small cell lung cancer (NSCLC), colon, central nervous system (CNS), melanoma, ovarian, renal, prostate, and breast cancer. Among all the compounds, 11, 12c, 12d, 12f, and 12j are active against different cancer cell lines. Between all the cell lines, compounds 12c, 12d, 12f, 12j, and 11 showed good inhibitory activity against renal cancer cell lines. From the five-dose study, based on IC₅₀ values, the order of activity of compounds against renal cancer cell lines was found to be 12c > 12f > 12c > 12j > 11 with 12c being the most potent, was better than sunitinib and sorafenib. Having been recognized as initial hits, these substances need additional pharmacological investigation.