Abstract

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.

Highlights

  • Schistosomiasis, leishmaniasis, and human African trypanosomiasis (HAT) are common neglected parasitic infections that affect people in sub-Saharan Africa (SSA) and together produce a huge disease burden in the region [1,2,3]

  • We described the detection, isolation, and characterization of Paenidigyamycin A (2) (Figure S12), a potent antiparasitic imidazole alkaloid from the Ghanaian Paenibacillus sp

  • Paenidigyamycin G (1) is one of the imidazole backbone alkaloids produced by the Ghanaian

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Summary

Introduction

Schistosomiasis, leishmaniasis, and human African trypanosomiasis (HAT) are common neglected parasitic infections that affect people in sub-Saharan Africa (SSA) and together produce a huge disease burden in the region [1,2,3]. Chemical profiling of the Kupchan sub-fractions using high resolution electrospray ionization liquid chromatography mass spectrometry (HRESI-LC-MS) and nuclear magnetic resonance spectroscopy (NMR) coupled with phytochemical screening on thin-layer chromatography (TLC) plates using Dragendorff and Ninhydrin reagents showed the FH to contain an alkaloid which was structurally related to 2. This alkaloid was the major metabolite seen in the FH fractions whenever strain DE2SH was Molbank 2019, 2019, x co-cultured other microbial the FH fraction was to reverse phase subjected towith reverse phase

Sediment Sample Collection Sites
Taxonomy of Strain DE2SH
H-1 H total
General Experimental Procedures
Culture of Parasites and Mammalian Cell Lines
Analysis of Cell Viability
Conclusions
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