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

• Main Authors: Aboagye Kwarteng Dofuor, Frederick Ayertey, Peter Bolah, Georgina Isabella Djameh, Kwaku Kyeremeh, Mitsuko Ohashi, Laud Kenneth Okine, Theresa Manful Gwira
• Format: Article
• Language: English
• Published: MDPI AG 2020-12-01
• Series: Biomolecules
• Subjects: skimmianine; 9-oxo-ODA; cell cycle; Trypanosoma brucei; Z. zanthoxyloides; oxidative stress
• Online Access: https://www.mdpi.com/2218-273X/10/12/1670

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<b>.</b> In this study, furoquinoline 4, 7, 8-trimethoxyfuro (2, 3-b) quinoline (compound <b>1</b>) and oxylipin 9-oxo-10, 12-octadecadienoic acid (compound <b>2</b>) were isolated from the plant species <i>Zanthoxylum zanthoxyloides </i>(Lam) Zepern and Timler (root), and their in vitro efficacy and mechanisms of action investigated in <i>Trypanosoma</i> <i>brucei</i> (<i>T. brucei</i>)<i>, </i>the species responsible for AT. Both compounds resulted in a selectively significant growth inhibition of <i>T. brucei</i> (compound <b>1</b>, half-maximal effective concentration EC₅₀ = 1.7 μM, selectivity indices SI = 74.9; compound <b>2</b>, EC₅₀ = 1.2 μM, SI = 107.3). With regards to effect on the cell cycle phases of <i>T. brucei</i>, only compound <b>1</b> 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 <i>T. brucei</i> cells in G0-G1 for both compounds. Moreover, both compounds resulted in the aggregation and distortion of the elongated slender morphology of <i>T. brucei</i>. Analysis of antioxidant potential revealed that at their minimum and maximum concentrations, the compounds exhibited significant oxidative activities in <i>T. brucei</i> (compound <b>1</b>, 22.7 μM Trolox equivalent (TE), 221.2 μM TE; compound <b>2</b>, 15.0 μM TE, 297.7 μM TE). Analysis of growth kinetics also showed that compound <b>1</b> exhibited a relatively consistent growth inhibition of <i>T. brucei </i>at different concentrations<i> </i>as compared to compound <b>2</b>. The results suggest that compounds <b>1</b> and <b>2</b> are promising antitrypanosomals with the potential for further development into novel AT chemotherapy.