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On-going Research Projects

Despite the tremendous success of modern medicine in many disease areas, there are still some diseases like HIV-AIDS, Ebola, polio and influenza that are without cures. This comes amidst the current widespread of new diseases and the spreading geographically of known diseases with increased virulence. Furthermore, the development of strong resistance to treatment by known diseases necessitates the discovery of new chemotherapeutic drugs with possible novel structural diversity and promiscuous mechanisms of action.

In order to ensure that, the drug discovery pipeline contains many drug prototypes that can be called upon at anytime for the development of new drugs, the world is heavily reliant on natural product research. Currently, at the Department of Chemistry, University of Ghana, my research involves “Investigation of Secondary Metabolites from Ghanaian Marine Organisms and their Bioactivity”. Several Ghanaian marine ecosystems offer a diverse array of invertebrates and most especially microbes that can serve as prospective sources of future drugs. Most of these habitats are either un- or underexplored for the possibility of isolating new bioactive metabolites which may serve as lead compounds for the discovery of new drugs. My investigations have already produced some very interesting results, a few of which are summarized below.

Marine Invertebrate

The Ghanaian sponge Axinella sp collected for the first time from the Gulf of Guinea yielded similar amounts of dakaramine, acetamide and a new hydroxylated acetate metabolite. The structures of these metabolites were elucidated by 1D and 2D NMR data interpretation. The halogens in dakaramine were detected by high performance liquid chromatography coupled with inductively coupled plasma and electrospray ionization mass spectrometry (HPLC-ICPMS/ESMS), a technique that allows for heteroatoms and metals in organic compounds to be detected specifically and with very high sensitivity. Cytotoxicity of dakaramine was assessed in vitro using two human cancer cell lines, human lymphocytic cell (Jurkat) and acute promyelocytic leukemia (HL60). This compound was found to be acutely toxic to these cell lines with IC50 values of 35.0 and 26.5 μg/ml respectively (J Chem Applications. 2014; 1(1): 4).

Marine Microbes

Fourty-six (46) different species of microbes including Actinomyces, Streptomyces, Salinospora, Verrucocispora and Micromonospora have been isolated from several mangrove patches in the Western region of Ghana including the rivers Butre and Amanzuri. While most of these microbes have shown promise as good sources of antimicrobials and cytotoxic agents, chemical profiling led to the prioritization of thirteen “talented” species including Micromonospora sp. K310, Verrucosispora sp. K51G and Micromonospora carbonacea

Micromonospora sp. K310

Micromonospora sp. K310 is the only Micromonospora species currently known to biosynthesise polycyclic tetramic acid macrolactam (PTM) butremycin which is the 3-hydroxyl derivative of the highly potent drug ikarugamycin. Also present in extracts of Micromonospora sp. K310 was the new compound PArTMTI which is the protonated aromatic tautomer of 5′-methylthioinosine (MTI). MTI is a molecule that has been implicated in a number of quorum sensing pathways involving Bacteria, Eucarya and Archaea (Mar. Drugs 2014, 12, 999-1012). 

Verrucosispora sp. K51G

Verrucosispora sp. K51G produces a new pyrazinone compound, butrepyrazinone that contains a novel amino acid moiety whose origin is not very clear. 13C feeding experiments are currently being conducted to discover the biosynthetic origin of this novel amino acid precursor (Mar. Drugs 2014, 12, 5197-5208).

 

Micromonospora carbonacea

Micromonospora carbonacea produces two novel aromatic ring antimicrobials for which the regiochemistry of their rings is currently under investigation.

 

Selected Publications

1) Kyeremeh, K., Acquah, K. S., Çamaş, M., Houssen, W., Tabudravu, J., Deng, H. and Jaspars, M. (2014). ''Butrepyrazinone, a new Pyrazinone with an unusual Methylation Pattern from a Ghanaian Verrucosispora sp. K51G ''. Marine Drugs, 12, 5197-5208.

2) Kyeremeh, K., Acquah, K. S., Appiah-Opong, R., Jaspars, M. and Deng, H. (2014). ''Effective detection, isolation and characterization of dakaramine from Ghanaian Axinella sp and bioactivity''. Journal of Chemistry and Applications, 1(1), 1-4.

3) Kyeremeh, K., Acquah, K. S., Sazak, A., Houssen, W., Tabudravu, J., Deng, H. and Jaspars, M. (2014). ''Butremycin, the 3-Hydroxyl Derivative of Ikarugamycin and a Protonated Aromatic Tautomer of 5′-Methylthioinosine from a Ghanaian Micromonospora sp. K310''. Marine Drugs, 12, 999-1012.

4) Deng, H., Ma, L., Bandaranayaka, N., Qin, Z., Mann, G., Kyeremeh, K., Yu, Y., Shepherd, T., Naismith, J. H. and O’Hagan, D. (2014). ''Identification of Fluorinases from Streptomyces sp. MA37, Norcardia brasiliensis, and Actinoplanes sp. N902-109 by Genome Mining''. ChemBioChem, 15, 364-368.

5) Kyeremeh, K., Agbemafo, F. W. and Appiah-Opong, R. (2013). ''Quantitative analysis of chemical contaminants in Ghanaian herbal alcoholic bitters''.  International Journal of Chemistry and Applications, 5(2), 153-167.

6) Kyeremeh, K., Asamoah, O., Botchie, S. K., Tuffour, I., Uto, T. and Appiah-Opong, R. (2013). ''Bioactivity data for eunicellin-based diterpenes isolated from Acalycigorgia sp''.  International Journal of Applied Chemistry, 9(2), 141-150.

7) Adamafio, N. A., Kyeremeh, K., Matey, A., Cheetham, M. and Kolawole, O. (2013). ''In situ degradation of cocoa (Theobroma cacao) pod husk theobromine by Candida krusei''.  International Journal of Biotechnology and Biochemistry, 9(1), 135-144.

8) Adamafio, N. A., Kyeremeh, K., Datsomor, A. and Osei-Owusu, J. (2013). ''Cocoa pod ash pre-treatment of wawa (Triplochitin scleroxylon) and sapele (Entandrophragma cylindricum) sawdust: Fourier transform infrared spectroscopic characterization of lignin''. Asian Journal of Scientific Research, 6(4), 812-818.

9) Qin, Z., McNee, D., Gleisner, H., Raab, A., Kyeremeh, K., Jaspars, M., Krupp, E., Deng, H. and Feldmann, J. (2012). ''Fluorine speciation analysis using reverse phase liquid chromatography coupled off-line to continuum source molecular absorption spectrometry (CS-MAS): Identification and quantification of novel fluorinated organic compounds in environmental and biological samples''. Analytical Chemistry, 84, 6213-6219.

10) Kyeremeh, K., Baddeley, T., Stein, B. and Jaspars, M. (2006). ''A homologous series of eunicellin-based diterpenes from Acalycigorgia sp. characterised by tandem mass spectrometry''. Tetrahedron, 62, 8770-78.

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