Betulinic acid and glycyrrhetinic acid derived piperazinyl spacered rhodamine B conjugates are highly cytotoxic and necrotic

Pentacyclic triterpene-piperazine-rhodamine B conjugates with ursane or oleanane backbones have been shown in the past to be highly cytotoxic thereby acting as mitocans. Starting from betulinic acid or glycyrrhetinic acid, new analogues were now made available, and their cytotoxic activity was investigated employing several human tumor cell lines [A375 (melanoma), HT29 (colorectal carcinoma), MCF-7 (breast adenocarcinoma), A2780 (ovarian carcinoma), and for comparison NIH 3T3 (non-malignant fibroblasts)]. For these conjugates it has been established that the linking position at ring E governs the magnitude of cytotoxicity. These conjugates were still highly cytotoxic but significantly less cytotoxic than those holding a oleanane skeleton. Staining experiments showed the rhodamine B conjugates as necrotic compounds and to act as mitocans. The most active compound (8) held an EC50 = 0.04 mu M for A2780 ovarian carcinoma cells.

Automated summary

New analogues of pentacyclic triterpene-piperazine-rhodamine B conjugates were synthesized from betulinic acid or glycyrrhetinic acid, and their cytotoxic activity was examined. The results showed that the linking position at ring E determines the magnitude of cytotoxicity. These conjugates were highly cytotoxic, acting as necrotic compounds and mitocans.