Planta Medica International Open 2017; 4(S 01): S1-S202
DOI: 10.1055/s-0037-1608114
Poster Session
Georg Thieme Verlag KG Stuttgart · New York

STEROIDAL ALKALOIDS AS POTENT AGENTS AGAINST Trypanosoma brucei rhodesiense

CO Nnadi
1   Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Münster, PharmaCampus,Corrensstraße 48, D-48149, Münster, Germany
2   Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria Nsukka, 40001 Nsukka, Enugu State, Nigeria
,
NJ Nwodo
2   Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria Nsukka, 40001 Nsukka, Enugu State, Nigeria
,
M Kaiser
3   Swiss Tropical and Public Health Institute (Swiss TPHI), Basel, Switzerland
4   University of Basel, Socinstr. 57, Basel CH-4051, Basel, Switzerland
,
R Brun
3   Swiss Tropical and Public Health Institute (Swiss TPHI), Basel, Switzerland
4   University of Basel, Socinstr. 57, Basel CH-4051, Basel, Switzerland
,
J Schmidt Thomas
1   Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Münster, PharmaCampus,Corrensstraße 48, D-48149, Münster, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
24 October 2017 (online)

 

Against the backdrop of our previous preliminary report on steroid alkaloids with promising antitrypanosomal activity from the leaves of West African Holarrhena africana [1], we have extended our search for such alkaloids to the stem bark. Bioactivity-guided isolation by repeated column chromatographic separation and purification of various alkaloidal fractions yielded six (1 – 6) steroidal alkaloids from the leaves [1], and eleven (7 – 17) steroidal alkaloids as well as one (18) nitrogen-free steroid from the stem bark. The structures were resolved by comparison of HRMS, 1D and 2D NMR spectra with reported data [2, 3]. All compounds were tested in vitro against Trypanosoma brucei rhodesiense and for cytotoxicity to mammalian cells (L6 cell line) and some structure-activity relationships became evident. The presence of a basic amino group at position 3 was found to be necessary for high antitrypanosomal activity of the steroid alkaloids. Pairwise comparison of the IC 50 values (µM) of 1 (0.40 ± 0.28) and 3 (0.08 ± 0.01), 12 (0.42 ± 0.09) and 13 (0.17 ± 0.11), 15 (1.66 ± 0.39) and 14 (0.12 ± 0.08) showed that monomethylation at the 3-amino group represents an optimum for antitrypanosomal activity. Comparison of the IC 50 values of 4 (1.20 ± 0.75) and 5 (0.67 ± 0.03) furthermore indicates that the C-3β amino substitution enhances activity. Overall, antitrypanosomal potency increases in the order O<NH<nh2<N(CH<n(ch3)2<NHCH<nhch3 with respect to substitution at C-3. The antitrypanosomal activities of these steroid alkaloids have not been reported before. Further studies on structure-activity relationships in terms of QSAR are currently in progress and will represent the basis for eventual lead optimization.</nhch</n(ch</nh

[1] Nnadi CO, Nwodo NJ, Brun R, Kaiser M, Schmidt TJ. Planta Medica. 2016; 82(S 01):S1-S381.

[2] Zirihi GN, Grellier P, Guede-Guina F, Bodo B, Mambu L. Bioorg Med Chem Lett. 2005; 15:2637 – 2640.

[3] Leboeuf M, Cavé A, Goutarel R. Ann Pharm Fr. 1969; 27:217 – 28.