Developing an Amide-Spacered Triterpenoid Rhodamine Hybrid of Nano-Molar Cytotoxicity Combined with Excellent Tumor Cell/Non-Tumor Cell Selectivity

Asiatic acid, a pentacyclic triterpene, was converted into a series of piperazinyl, homopiperazinyl, and 1,5-diazocinyl spacered rhodamine conjugates, differing in the type of spacer and the substitution pattern on the rhodamine moiety of the hybrids. The compounds were tested for cytotoxic activity in SRB assays and compound 12, holding an EC50 of 0.8 nM, was the most cytotoxic compound of this series, but compound 18 (containing a ring expanded 1,5-diazocinyl moiety and n-propyl substituents on the rhodamine) was the most selective compound exhibiting a selectivity factor of almost 190 while retaining high cytotoxicity (EC50 = 1.9 nM, for A2780 ovarian carcinoma).

Automated summary

In this study, Asiatic acid was converted into different types of rhodamine conjugates with piperazinyl, homopiperazinyl, and 1,5-diazocinyl spacers. The compounds were tested for cytotoxic activity, and compound 12 showed the highest cytotoxicity with an EC50 of 0.8 nM. However, compound 18, with a ring expanded 1,5-diazocinyl moiety and n-propyl substituents, exhibited the highest selectivity with a selectivity factor of almost 190 while maintaining high cytotoxicity (EC50 = 1.9 nM for A2780 ovarian carcinoma).