Paenidigyamycin, A Novel Antiparasitic Alkaloid From The Ghanaian Paenibacillus Polymyxa Strain De2sh

ABSTRACT

There is an ever-growing interest in the Paenibacillus genus as a result of reports that strains belonging to this genus have several important properties. These properties include promotion of plant growth, bioremediation and the biosynthesis of structurally intriguing molecules with unrivalled biological activities and mechanisms of action. However, the agricultural applications of the aforementioned molecules far outweigh their use in medicine. In this current report, a novel Paenibacillus polymyxa strain designated DE2SH isolated from the extremely biodiverse wetlands of the Brong-Ahafo Region of Ghana was thoroughly investigated for its metabolite biosynthesis and biological activity potential.

A screening and de-replication process involving HRESI/HPLC-MSn and the AntiMarin database revealed the presence of novel chemistry. Hence, large scale cultures of this biosynthetically talented strain was prepared in ISP2 and TSBY media. Total crude extracts obtained were subjected to a modification of the Kupchan solvent partitioning process to afford FH, FD, FM and WB fractions for both cultures. Subsequent spectrometric and spectroscopic screening of these fractions led to the prioritization of DE2SH-TSBY-FM. It was deduced that this fraction contained the compounds of interest in appreciably pure and isolable amounts. DE2SH-TSBY-FM was further fractionated by size-exclusion chromatography using Sephadex LH-20 as stationary phase to afford six fractions. These fractions were then investigated using spectroscopic and phytochemical screening methods which led to the prioritization of Sephadex fraction C. This fraction was purified using HPLC fitted with a biphenyl column to yield seven fractions, six of which were found to contain novel alkaloids designated the Paenidigyamycins.

1D and 2D NMR data were acquired and an attempt was made to characterize Paenidigyamycin C. However, the lack of spin systems in the central part of the molecule made the unambiguous

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determination of its complete structure very challenging. More spectroscopic data will be required to validate the structure of Paenidigyamicin C proposed in this thesis. Subsequent biological activity tests in a number of bio-assays showed the compound to possess excellent anti-leishmania activity against L. major (IC50 0.23μM). The compound however showed minimal activity against T. mobilensis.