Digyaindoleacid A: 2-(1-(4-hydroxyphenyl)-3-oxobut-1-en-2-yloxy)-3-(1H-indol-3-yl)propanoic acid, a novel indole alkaloid

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 927/4 GUTat10.1, 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 927/4 GUTat10.1. 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).