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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 &asymp, 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 &mu, M compared to the standard diminazene aceturate (IC50 = 1.86 &mu, M). 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 &mu, M) produced weak antileishmanial activity when tested against Leishmania donovani (Laveran and Mesnil) Ross (D10).

The Ghanaian Paenibacillus sp. DE2SH (GenBank Accession Number: MH091697) is a prolific producer of potent antiparasitic alkaloids. Further detailed study of the culture broth of this strain produced the compound Paenidigyamycin G (1), which is a derivative of the known antiparasitic compound Paenidigyamycin A (2). Compound (1) was isolated on HPLC at tR ≈ 37.5 min and its structure determined by IR, UV, MS, 1D, and 2D-NMR data. Compound 1 produced weak to moderate antileishmanial and antitrypanosomal activity when tested against Leishmania donovani (Laveran and Mesnil) Ross (D10) and Trypanosoma brucei subsp. brucei strain GUTat 3.1 with IC50 = 115.41 and 28.75 μM, respectively. This result is interesting since the parent compound 2 is known to possess consistent and potent antiparasitic activity. However, 1 displayed a promising selectivity profile towards T. brucei subsp. brucei due to its relatively low toxicity against normal mouse macrophages RAW 264.7 cells (SI = 8.70). Given that compound 1 is also the main metabolite found in the hexane fraction of all extracts produced by Paenibacillus sp. DE2SH when it is co-cultured with other bacteria strains, it must possess some unique biological functions which should make it an excellent candidate for further biological activity screening in other bioassays.

Leishmaniasis is an infectious disease transmitted by the sand fly. It is caused by over 20 different species of Leishmania and has affected over 14 million people worldwide. One of the main forms of control of leishmaniasis is chemotherapy, but this is limited by the high cost and/or toxicity of available drugs. We previously found three novel compounds with an iridoid tetracyclic skeleton to have activity against trypanosome parasites. In this study, we determined the activity of the three anti-trypanosome compounds against Leishmania using field strain, 010, and the lab strain Leishmania hertigi. The minimum inhibitory concentration (MIC) of the compounds against 010 was determined by microscopy while the IC50 of compounds against L. hertigi was determined by fluorescence-activated cell sorting with Guava viacount analysis. We found two of the three compounds, molucidin and ML-F52, to have anti-Leishmania activity against both strains. The fluor-microscope observation with DAPI stain revealed that both Molucidin and ML-F52 induced abnormal parasites with two sets of nucleus and kinetoplast in a cell, suggesting that compounds might inhibit cytokinesis in Leishmania parasites. Molucidin and ML-F52 might be good lead compounds for the development of new anti-Leishmania chemotherapy.