Paenidigyamycin A, Potent Antiparasitic Imidazole Alkaloid from the Ghanaian Paenibacillus sp. DE2SH
Enoch Osei,
Samuel Kwain,
Gilbert Tetevi Mawuli,
Abraham Kwabena Anang,
Kofi Baffour-Awuah Owusu,
Mustafa Camas,
Anil Sazak Camas,
Mitsuko Ohashi,
Cristina-Nicoleta Alexandru-Crivac,
Hai Deng,
Marcel Jaspars,
Kwaku Kyeremeh
Affiliations
Enoch Osei
Marine and Plant Research Laboratory of Ghana, Department of Chemistry, School of Physical and Mathematical Sciences, University of Ghana, P.O. Box LG 56, Legon-Accra, Ghana
Samuel Kwain
Marine and Plant Research Laboratory of Ghana, Department of Chemistry, School of Physical and Mathematical Sciences, University of Ghana, P.O. Box LG 56, Legon-Accra, Ghana
Gilbert Tetevi Mawuli
Marine and Plant Research Laboratory of Ghana, Department of Chemistry, School of Physical and Mathematical Sciences, University of Ghana, P.O. Box LG 56, Legon-Accra, Ghana
Abraham Kwabena Anang
Department of Parasitology, Noguchi Memorial Institute for Medical Research, University of Ghana, P.O. Box LG 581, Legon-Accra, Ghana
Kofi Baffour-Awuah Owusu
Department of Parasitology, Noguchi Memorial Institute for Medical Research, University of Ghana, P.O. Box LG 581, Legon-Accra, Ghana
Mustafa Camas
Department of Bioengineering, Munzur University, 62000 Tunceli, Turkey
Anil Sazak Camas
Department of Bioengineering, Munzur University, 62000 Tunceli, Turkey
Mitsuko Ohashi
Section of Environmental Parasitology, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
Cristina-Nicoleta Alexandru-Crivac
Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Old Aberdeen, AB24 3UE Scotland, UK
Hai Deng
Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Old Aberdeen, AB24 3UE Scotland, UK
Marcel Jaspars
Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, Old Aberdeen, AB24 3UE Scotland, UK
Kwaku Kyeremeh
Marine and Plant Research Laboratory of Ghana, Department of Chemistry, School of Physical and Mathematical Sciences, University of Ghana, P.O. Box LG 56, Legon-Accra, Ghana
A new alkaloid paenidigyamycin A (1) was obtained from the novel Ghanaian Paenibacillus sp. isolated from the mangrove rhizosphere soils of the Pterocarpus santalinoides tree growing in the wetlands of the Digya National Park, Ghana. Compound 1 was isolated on HPLC at tR = 37.0 min and its structure determined by MS, 1D, and 2D-NMR data. When tested against L. major, 1 (IC50 0.75 µM) was just as effective as amphotericin B (IC50 0.31 µM). Against L. donovani, 1 (IC50 7.02 µM) was twenty-two times less active than amphotericin B (IC50 0.32 µM), reinforcing the unique effectiveness of 1 against L. major. For T. brucei brucei, 1 (IC50 0.78 µM) was ten times more active than the laboratory standard Coptis japonica (IC50 8.20 µM). The IC50 of 9.08 µM for 1 against P. falciparum 3d7 compared to artesunate (IC50 36 nM) was not strong, but this result suggests the possibility of using the paenidigyamycin scaffold for the development of potent antimalarial drugs. Against cercariae, 1 showed high anticercaricidal activity compared to artesunate. The minimal lethal concentration (MLC) and minimal effective concentration (MEC) of the compound were 25 and 6.25 µM, respectively, while artesunate was needed in higher quantities to produce such results. However, 1 (IC50 > 100 µM) was not active against T. mobilensis.
