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Screening of Agelasine D and analogs for inhibitory activity against pathogenic protozoa; identification of hits for visceral Leishmaniasis and Chagas disease
Vik, A.; Proszenyak, A.; Vermeersch, M.; Cos, P.; Maes, L.; Gundersen, L.-L. (2009). Screening of Agelasine D and analogs for inhibitory activity against pathogenic protozoa; identification of hits for visceral Leishmaniasis and Chagas disease. Molecules 14(1): 279-288. https://dx.doi.org/10.3390/molecules14010279
In: Molecules. MDPI: Basel. e-ISSN 1420-3049
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| Trefwoord |
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| Author keywords |
Agelasine; Antiprotozoal; Chagas disease; Visceral leishmaniasis |
| Auteurs | | Top |
- Vik, A.
- Proszenyak, A.
- Vermeersch, M.
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- Cos, P.
- Maes, L.
- Gundersen, L.-L.
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| Abstract |
There is an urgent need for novel and improved drugs against several tropical diseases caused by protozoa. The marine sponge (Agelas sp.) metabolite agelasine D, as well as other agelasine analogs and related structures were screened for inhibitory activity against Plasmodium falciparum, Leishmania infantum, Trypanosoma brucei and T. cruzi, as well as for toxicity against MRC-5 fibroblast cells. Many compounds displayed high general toxicity towards both the protozoa and MRC-5 cells. However, two compounds exhibited more selective inhibitory activity against L. infantum (IC50 <0.5 mg/mL) while two others displayed IC50 <1 mg/mL against T. cruzi in combination with relatively low toxicity against MRC-5 cells. According to criteria set up by the WHO Special Programme for Research & Training in Tropical Diseases (TDR), these compounds could be classified as hits for leishmaniasisand for Chagas disease, respectively. Identification of the hits as well as other SAR data from this initial screening will be valuable for design of more potent and selective potential drugs against these neglected tropical diseases |
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