Semi-synthesis and cytotoxicity evaluation of pyrimidine, thiazole, and indole analogues of argentatins A-C from guayule (Parthenium argentatum) resin

Argentatins A-C (1-3), the major cycloartane-type triterpenoids of guayule resin, a byproduct of commercial rubber production, were converted into their pyrimidine (7-12), thiazole (13-15), and indole (16-18) analogues by a molecular hybridization approach. The cytotoxic activities of these fused heterocyclic analogues 7-18 were compared with those of argentatins A-C (1-3) against a panel of three sentinel human cancer cell lines [NCI-H460 (non-small cell lung), MCF-7 (breast adenocarcinoma), and SF-268 (central nervous system glioma)], and normal human fibroblast (WI-38) cells. The cytotoxicity data suggest that the pyrimidine analogues 7 and 8 (derived from 1), 9 and 10 (derived from 2), and 12 (derived from 3) had significantly enhanced activity compared to the parent compounds or their thiazole (13-15) and indole (16-18) analogues. These findings indicate that triterpenoid constituents of guayule resin may be exploited to obtain value-added products with potential applications in anticancer drug discovery.

Automated summary

Argentatins A-C, the major cycloartane-type triterpenoids in guayule resin, were converted into pyrimidine, thiazole, and indole analogues. The cytotoxic activities of these analogues were compared with the parent compounds against cancer cell lines and normal cells, showing enhanced activity in the pyrimidine analogues. These findings suggest the potential of triterpenoid constituents in guayule resin for anticancer drug discovery.