Cyclopeptide Alkaloids from Hymenocardia acida

Abstract

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 μM, the most active one being hymenocardine N-oxide (3), with an IC50 value of 12.2 ± 6.6 μM. Compounds 2-4 were found not to be cytotoxic against MRC-5 cells (IC50 > 64.0 μM), but hymenocardine (1) showed some cytotoxicity, with an IC50 value of 51.1 ± 17.2 μM.

Antiplasmodial Activity, Cytotoxicity and Structure-Activity Relationship Study of Cyclopeptide Alkaloids

“…The in vitro antiplasmodial activity against P. falciparum strain K1 and the cytotoxicity against MRC-5 cells was determined for ten cyclopeptide alkaloids, isolated from the stem bark of Ziziphus nummularia , Ziziphus spina-christi , Ziziphus jujuba , and the root of Hovenia dulcis , all belonging to the Rhamnaceae family, and the results are shown in Table 1 . The results that were previously reported for cyclopeptide alkaloids isolated from the root bark of H. acida (Phyllanthaceae) and the roots of Z. oxyphylla (Rhamnaceae) [ 6 , 7 ] are also included in this table. The highest antiplasmodial activity was found for spinanine-B ( 3 ), with an IC 50 value of 2.1 μM and without cytotoxic effects in concentrations of 64.0 μM or less.…”

“…Nummularine-B was found to be moderately active (IC 50 value of 10.3 μM) against Plasmodium falciparum , but not mauritine-L and nummularine-B methiodide [ 5 ]. Our research group has previously reported the antiplasmodial activity of cyclopeptide alkaloids from Hymenocardia acida and Ziziphus oxyphylla [ 6 , 7 ]. Based on these results, some preliminary conclusions concerning their SAR (structure-activity relationship) were drawn, but given the fact that the number of compounds tested in each of these studies was relatively small, it was not possible to draw definite conclusions.…”

“…In the present paper, the antiplasmodial and cytotoxic activities of ten cyclopeptide alkaloids are reported, of which only the antiplasmodial activity of nummularine-B was reported previously [ 5 ]. These results were then combined with previous data obtained by our group in the same test conditions for nine other cyclopeptide alkaloids from H. acida and Z. oxyphylla [ 6 , 7 ], in order to perform a SAR study, and to identify the molecular characteristics that can account for high antiplasmodial activity.…”

Alkaloids from Plants with Antimalarial Activity: A Review of Recent Studies

“…Compound 45 together with others shows high and specific activities against P. falciparum [39] Evidence-Based Complementary and Alternative Medicine A new alkaloid, tavoyanine A (56), and other known alkaloids, roemerine (57), laurolitsine (58), boldine (59), and sebiferine (60) Aporphine alkaloids (56)(57)(58)(59) and morphinandienone (60) Leaf 1.10. Quinoline Alkaloids.…”

New bioactive cyclopeptide alkaloids with rare terminal unit from the root bark ofZiziphus cambodiana

“…None of the compounds were toxic to the non-cancerous Vero cells, except for 6, which showed weak action with an IC 50 of 48.2 mM. To date, only two studies on the in vitro cytotoxicity of natural rhamnaceous cyclopeptide alkaloids have been reported, 38,49 although the weak activity of some representative synthetic 13-and 15-membered ring cyclopeptides was described recently. 50…”