Cyclopeptide Alkaloids from Hymenocardia acida

Four cyclopeptide alkaloids (1-4) were isolated from the root bark of Hymenocardia acida by means of semipreparative HPLC with DAD and ESIMS detection and conventional separation methods. Structure elucidation was performed by spectroscopic means. In addition to the known compound hymenocardine (1), three other alkaloids were isolated for the first time from a natural source. These included a hymenocardine derivative with a hydroxy group instead of a carbonyl group that was named hymenocardinol (2), as well as hymenocardine N-oxide (3) and a new cyclopeptide alkaloid containing an unusual histidine moiety named hymenocardine-H (4). The isolated cyclopeptide alkaloids were tested for their antiplasmodial activity and cytotoxicity. All four compounds showed moderate antiplasmodial activity, with IC50 values ranging from 12.2 to 27.9 mu M, the most active one being hymenocardine N-oxide (3), with an IC50 value of 12.2 +/- 6.6 mu M. Compounds 2-4 were found not to be cytotoxic against MRC-5 cells (IC50 > 64.0 mu M), but hymenocardine (1) showed some cytotoxicity, with an IC50 value of 51.1 +/- 17.2 mu M.