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Antimalarial drug interactions of compounds isolated from Kigelia africana (Bignoniaceae) and their synergism with artemether, against the multidrug-resistant W2mef Plasmodium falciparum strain

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Abstract

For decades, drug resistance has been the major obstacle in the fight against malaria, and the search for new drugs together with the combination therapy constitutes the major approach in responding to this situation. The present study aims at assessing the in vitro antimalarial activity of four compounds isolated from Kigelia africana stem bark (atranorin - KAE1, specicoside - KAE7, 2β,3β,19α-trihydroxy-urs-12-20-en-28-oic acid – KAE3, and p-hydroxy-cinnamic acid – KAE10) and their drug interactions among themselves and their combination effects with quinine and artemether. The antiplasmodial activity and drug interactions were evaluated against the multidrug-resistant W2mef strain of Plasmodium falciparum using the parasite lactate dehydrogenase assay. Three of the four compounds tested were significantly active against W2mef: specicoside (IC50 = 1.02 ± 0.17 μM), 2β,3β,19α-trihydroxy-urs-12-en-28-oic acid (IC50 = 1.86 ± 0.15 μM) and atranorin (IC50 = 1.78 ± 0.18 μM), whereas p-hydroxy-cinnamic acid showed a weak activity (IC50 = 12.89 ± 0.87 μM). A slight synergistic effect was observed between atranorin and 2β,3β,19α-trihydroxy-urs-12-en-28-oic acid (Combination index, CI = 0.82) whereas the interaction between specicoside and p-hydroxy-cinnamic acid were instead antagonistic (CI = 2.67). All the three compounds showed synergistic effects with artemether, unlike the slight antagonistic interactions of atranorin and 2β,3β,19α-trihydroxy-urs-12-en-28-oic acid in combination with quinine. K. africana compounds are therefore likely to serve as leads in the development of new partner drugs in artemether-based combination therapy.

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Acknowledgements

This work received financial support in the form of research grants awarded to Professor Vincent P.K. Titanji by the International Programme in the Chemical Sciences (IPICS, CAM:01) and Microsoft Corporation, and a research grant from the International Foundation for Science (IFS) awarded to Dr. Mathieu Tene (RGA no. F/4238-1).

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Authors and Affiliations

  1. Biotechnology Unit, University of Buea, P.O. Box 63, Buea, South West Region, Cameroon

    Denis Zofou & Vincent P. K. Titanji

  2. Laboratory of Natural Products Chemistry, University of Dschang, Dschang, West Region, Cameroon

    Mathieu Tene & Pierre Tane

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  1. Denis Zofou
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  2. Mathieu Tene
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  3. Pierre Tane
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  4. Vincent P. K. Titanji
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Correspondence to Vincent P. K. Titanji.

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Zofou, D., Tene, M., Tane, P. et al. Antimalarial drug interactions of compounds isolated from Kigelia africana (Bignoniaceae) and their synergism with artemether, against the multidrug-resistant W2mef Plasmodium falciparum strain. Parasitol Res 110, 539–544 (2012). https://doi.org/10.1007/s00436-011-2519-9

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