Trypanocidal and leishmanicidal activity of six limonoids
- PDF / 802,189 Bytes
- 6 Pages / 595.276 x 790.866 pts Page_size
- 74 Downloads / 177 Views
NOTE
Trypanocidal and leishmanicidal activity of six limonoids Dietmar Steverding1 · Lazare S. Sidjui2,3 · Éden Ramalho Ferreira4,5 · Bathelemy Ngameni6 · Gabriel N. Folefoc3 · Valérie Mahiou‑Leddet7 · Evelyne Ollivier7 · G. Richard Stephenson8 · Thomas E. Storr8 · Kevin M. Tyler4 Received: 3 February 2020 / Accepted: 31 March 2020 © The Author(s) 2020
Abstract Six limonoids [kotschyienone A and B (1, 2), 7-deacetylgedunin (3), 7-deacetyl-7-oxogedunin (4), andirobin (5) and methyl angolensate (6)] were investigated for their trypanocidal and leishmanicidal activities using bloodstream forms of Trypanosoma brucei and promastigotes of Leishmania major. Whereas all compounds showed anti-trypanosomal activity, only compounds 1–4 displayed anti-leishmanial activity. The 50% growth inhibition ( GI50) values for the trypanocidal and leishmanicidal activity of the compounds ranged between 2.5 and 14.9 μM. Kotschyienone A (1) was found to be the most active compound with a minimal inhibition concentration (MIC) value of 10 μM and G I50 values between 2.5 and 2.9 μM. Only compounds 1 and 3 showed moderate cytotoxicity against HL-60 cells with MIC and G I50 values of 100 μM and 31.5–46.2 μM, respectively. Compound 1 was also found to show activity against intracellular amastigotes of L. major with a GI50 value of 1.5 μM. The results suggest that limonoids have potential as drug candidates for the development of new treatments against trypanosomiasis and leishmaniasis. Keywords Limonoids · African trypanosomiasis · Trypanosoma brucei · Leishmaniasis · Leishmania major
Introduction Trypanosomiasis and leishmaniasis are devastating diseases for both humans and their domestic animals. Trypanosome parasites cause sleeping sickness in humans and nagana disease in cattle in Africa and Chagas disease in humans in Latin America [1, 2]. The different Leishmania parasites cause a variety of clinical conditions (localised skin lesions, Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11418-020-01408-7) contains supplementary material, which is available to authorized users.
mucosal ulcers, and internal organ damage) in humans worldwide [3]. These parasites are kinetoplastid protozoans and are transmitted to their mammalian host by insect vectors. Treatment of these parasitoses relies on chemotherapy but only a few drugs are available. However, most of the drugs are not well tolerated or show toxic side effects, are not very effective, and are being increasingly subject to drug resistance. Therefore, effective and better-tolerated chemotherapies are urgently needed for the treatment of trypanosomiasis and leishmaniasis.
* Dietmar Steverding [email protected]
4
BioMedical Research Centre, Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK
* Bathelemy Ngameni [email protected]
5
Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
6
Department of P
Data Loading...
