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.