New purine-triazole hybrids as potential anti-breast cancer agents: synthesis, antiproliferative activity, and ADMET in silico study

Two series of new 1,2,3-triazole-purine hybrids were synthesized in considerable yields (up to 87%), starting from benzyl azides and purine alkynes, via 1,3-dipolar cycloaddition reaction catalyzed with Cu(I). The first (7a-k) and second (8a-k) series of hybrids employed kinetin and adenine as precursors, respectively. All synthesized compounds were evaluated in vitro for their antiproliferative activity against two breast cancer cell lines (MCF-7 and MDA-MB-231) and a non-tumor cell line (MCF-10A) to estimate their selectivity. From the twenty-two synthesized compounds, eight (4, 7a-e, 7 h and 8a) were active against both tumor cell lines, especially the kinetin derivatives, which displayed better results than the adenine derivatives. The original kinetin molecule was not active, suggesting that structural changes in its derivatives were favorable to induce cytotoxic effects in the tested cells. Compounds 7c and 7d were the most active, with IC50 of 22.3 mu M and 22.9 mu M for MCF-7, and IC50 of 9.3 mu M and 16.7 mu M for MDA-MB-231, respectively. In addition, the ADMET in silico study indicated that the active compounds (4, 7a-e, 7 h and 8a) presented drug-like similarities and a potential use as anticancer agents.

Automated summary

Two series of new 1,2,3-triazole-purine hybrids were successfully synthesized in high yields using benzyl azides and purine alkynes as starting materials. The compounds were evaluated for their antiproliferative activity against breast cancer cell lines, with the kinetin derivatives showing better efficacy than the adenine derivatives. Compound 7c and 7d exhibited the highest activity against the tested cancer cells. In silico studies indicated that the active compounds have drug-like properties and potential as anticancer agents.