Nano-assembly of cytotoxic amides of moronic and morolic acid†
Moronic acid and morolic acid, less frequently studied plant triterpenoids, were subjected to derivation with several structural modifiers, namely, piperazine-, pyrazine-, 1H-indole- and L-methionine-based compounds. Derivation was targeted to design and prepare novel compounds capable of nano-assembling and/or displaying cytotoxicity. Formation of nanostructures has been proven for several novel target compounds that formed different types of nanostructures, either in chloroform or in water. Isometric nanoparticles with broad size distributions (12 and 25), distorted single sheets (23) or very large thin warped films (13) were formed in chloroform solutions. Sheet-like nanostructures (12 and 23), and sphere-like nanostructures (hydrogen bonding connected nanoparticles; 3, 5, 13, 21 and 25) were formed in water suspensions. Cytotoxicity was also investigated and compared with that of the parent triterpenoids, showing enhanced effect of 18 that was the most successful derivative of the prepared series with sufficient balance between its cytotoxicity in CEM (IC50 = 11.7 ± 2.4 μM), HeLa (IC50 = 9.0 ± 0.7 μM) and G-361 (IC50 = 10.6 ± 5.5 μM) cancer cell lines, and toxicity in BJ (IC50 = 43.3 ± 1.5 μM). The calculated selectivity index values for 18 are SI = 3.9 (CEM), 4.8 (HeLa) and 4.4 (G-361). Additional compounds displaying cytotoxicity were 5, 7, 9 and 15, all of them showed comparable cytotoxicity with 18, in the investigated cancer cell lines; however, they were more toxic in BJ than 18.