Abstract
Digyaindoleacid A (1) is one of the novel alkaloids produced by the Ghanaian Paenibacillus sp. DE2SH (GenBank Accession Number: MH091697) isolated from the mangrove rhizosphere soils of the Pterocarpus santalinoides tree growing in the wetlands of the Digya National Park, Brong Ahafo Region, Ghana. This compound was isolated on HPLC at tR ≈ 60 min and its structure determined by MS, 1D, and 2D-NMR data. When tested against Trypanosoma brucei subsp. brucei strain GUTat 3.1, 1 produced a half-maximal inhibitory concentration (IC50) 5.21 μM compared to the standard diminazene aceturate (IC50 = 1.86 μM). In the presence of normal mouse macrophages RAW 264.7, 1 displayed a higher selectivity towards T. brucei subsp. brucei (selectivity indices (SI) = 30.2) with low toxicity. This result is interesting given that the drug diminazene aceturate is considerably toxic and 1 is a natural product isolate. The structure of 1 incorporates the backbone of the amino acid tryptophan which is crucial in the metabolism of Trypanosoma brucei subsp. brucei strain GUTat 3.1. It is possible that 1, could interfere with the normal uptake and metabolism of tryptophan in the parasite. However, 1 (IC50 = 135.41 μM) produced weak antileishmanial activity when tested against Leishmania donovani (Laveran and Mesnil) Ross (D10).
Highlights
Buruli ulcer, Chagas disease, cysticercosis, dengue fever, Guinea worm, echinococcosis, fascioliasis, human African trypanosomiasis, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, rabies, schistosomiasis, soil transmitted helminths, trachoma and yaws represent the comprehensive and slow growing list of neglected tropical diseases (NTDs) worldwide [1]
The human anatomy affected by the current disease burden; heart, lungs, alimentary canal and central nervous system are severely affected by NTDs such as Chagas disease, trypanosomiasis, leishmaniasis and schistosomiasis
Digyaindoleacid A (1) is one of the alkaloids responsible for the antitrypanosomal activity shown by water (FM) and butanol/water (WB) extracts of the Ghanaian microbial strain Paenibacillus sp
Summary
Chagas disease, cysticercosis, dengue fever, Guinea worm, echinococcosis, fascioliasis, human African trypanosomiasis, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, rabies, schistosomiasis, soil transmitted helminths, trachoma and yaws represent the comprehensive and slow growing list of neglected tropical diseases (NTDs) worldwide [1]. The human anatomy affected by the current disease burden; heart, lungs, alimentary canal and central nervous system are severely affected by NTDs such as Chagas disease, trypanosomiasis, leishmaniasis and schistosomiasis. DE2SH (GenBank Accession Number: MH091697) in ISP2 fermentation media at pH 5.5, 28 ◦ C, 220 rpm and 14 days incubation produced crude extracts which possessed antiparasitic activity against trypanosomes, schistosomes and leishmania. Chemical profiling of these extracts using high resolution electrospray ionization liquid chromatography mass spectrometry (HRESI-LC-MS) and nuclear magnetic resonance spectroscopy (NMR) showed the presence of several alkaloids. Reverse phase HPLC of WB-SF6 led to the isolation of the potent antitrypanosomal agent digyaindoleacid A
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