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Three esters of rhodamine B (1–3) differing in their alkyl chain lengths as well as several rhodamine B amides (4–9) were synthesized in good yields and tested for their cytotoxicity in SRB assays employing several human tumor cell lines. The rhodamine B esters were unselective but showed cytotoxicity of as low as EC50 = 0.15 ± 0.02 µM. The rhodamine B amides were slightly less cytotoxic but showed good selectivity against MCF-7 and A2780 tumor cell lines. Especially a morpholinyl derivative 4 was ~20 time more cytotoxic for MCF-7 than for nonmalignant NIH 3T3 cells.

Due to their manifold biological activities, natural products such as triterpenoids have advanced to represent excellent leading structures for the development of new drugs. For this reason, we focused on the syntheses and cytotoxic evaluation of derivatives obtained from gypsogenin, hederagenin, and madecassic acid, cytotoxicity increased—by and large—from the parent compounds to their acetates. Another increase in cytotoxicity was observed for the acetylated amides (phenyl, benzyl, piperazinyl, and homopiperazinyl), but a superior cytotoxicity was observed for the corresponding rhodamine B conjugates derived from the (homo)-piperazinyl amides. In particular, a madecassic acid homopiperazinyl rhodamine B conjugate 24 held excellent cytotoxicity and selectivity for several human tumor cell lines. Thus, this compound was more than 10,000 times more cytotoxic than parent madecassic acid for A2780 ovarian cancer cells. We assume that the presence of an additional hydroxyl group at position C–6 in derivatives of madecassic, as well as the (2α, 3β) configuration of the acetates in ring A, had a beneficial effect onto the cytotoxicity of the conjugates, as well as onto tumor/non-tumor cell selectivity.

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