Isolation and Antitrypanosomal Characterization of Furoquinoline and Oxylipin from <i>Zanthoxylum zanthoxyloides</i>

Aboagye Kwarteng Dofuor; Frederick Ayertey; Peter Bolah; Georgina Isabella Djameh; Kwaku Kyeremeh; Mitsuko Ohashi; Laud Kenneth Okine; Theresa Manful Gwira

doi:10.3390/biom10121670

Biomolecules (Dec 2020)

Isolation and Antitrypanosomal Characterization of Furoquinoline and Oxylipin from <i>Zanthoxylum zanthoxyloides</i>

Aboagye Kwarteng Dofuor,
Frederick Ayertey,
Peter Bolah,
Georgina Isabella Djameh,
Kwaku Kyeremeh,
Mitsuko Ohashi,
Laud Kenneth Okine,
Theresa Manful Gwira

Affiliations

Aboagye Kwarteng Dofuor: West African Center for Cell Biology of Infectious Pathogens, University of Ghana, P.O. Box LG54, Legon, Accra, Ghana
Frederick Ayertey: Centre for Plant Medicine Research, P.O. Box 73, Mampong-Akuapem, Ghana
Peter Bolah: Centre for Plant Medicine Research, P.O. Box 73, Mampong-Akuapem, Ghana
Georgina Isabella Djameh: Department of Parasitology, Noguchi Memorial Institute for Medical Research, University of Ghana, P.O. Box LG 581, Legon, Accra, Ghana
Kwaku Kyeremeh: Department of Chemistry, University of Ghana, P.O. Box LG 56, Legon, Accra, Ghana
Mitsuko Ohashi: Department of Parasitology, Noguchi Memorial Institute for Medical Research, University of Ghana, P.O. Box LG 581, Legon, Accra, Ghana
Laud Kenneth Okine: West African Center for Cell Biology of Infectious Pathogens, University of Ghana, P.O. Box LG54, Legon, Accra, Ghana
Theresa Manful Gwira: West African Center for Cell Biology of Infectious Pathogens, University of Ghana, P.O. Box LG54, Legon, Accra, Ghana

DOI: https://doi.org/10.3390/biom10121670
Journal volume & issue: Vol. 10, no. 12
p. 1670

Abstract

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In the absence of vaccines, there is a need for alternative sources of effective chemotherapy for African trypanosomiasis (AT). The increasing rate of resistance and toxicity of commercially available antitrypanosomal drugs also necessitates an investigation into the mode of action of new antitrypanosomals for AT. In this study, furoquinoline 4, 7, 8-trimethoxyfuro (2, 3-b) quinoline (compound 1) and oxylipin 9-oxo-10, 12-octadecadienoic acid (compound 2) were isolated from the plant species Zanthoxylum zanthoxyloides (Lam) Zepern and Timler (root), and their in vitro efficacy and mechanisms of action investigated in Trypanosoma brucei (T. brucei), the species responsible for AT. Both compounds resulted in a selectively significant growth inhibition of T. brucei (compound 1, half-maximal effective concentration EC50 = 1.7 μM, selectivity indices SI = 74.9; compound 2, EC50 = 1.2 μM, SI = 107.3). With regards to effect on the cell cycle phases of T. brucei, only compound 1 significantly arrested the second growth-mitotic (G2-M) phase progression even though G2-M and DNA replication (S) phase arrest resulted in the overall reduction of T. brucei cells in G0-G1 for both compounds. Moreover, both compounds resulted in the aggregation and distortion of the elongated slender morphology of T. brucei. Analysis of antioxidant potential revealed that at their minimum and maximum concentrations, the compounds exhibited significant oxidative activities in T. brucei (compound 1, 22.7 μM Trolox equivalent (TE), 221.2 μM TE; compound 2, 15.0 μM TE, 297.7 μM TE). Analysis of growth kinetics also showed that compound 1 exhibited a relatively consistent growth inhibition of T. brucei at different concentrations as compared to compound 2. The results suggest that compounds 1 and 2 are promising antitrypanosomals with the potential for further development into novel AT chemotherapy.

Published in Biomolecules

ISSN: 2218-273X (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: https://www.mdpi.com/journal/biomolecules

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