Semi-Synthesis and Evaluation of Sargahydroquinoic Acid Derivatives as Potential Antimalarial Agents

• Published in: Medicines (Basel, Switzerland) Switzerland), 2019-04, Vol.6 (2), p.47
• Main Authors: Munedzimwe, Tatenda C, van Zyl, Robyn L, Heslop, Donovan C, Edkins, Adrienne L, Beukes, Denzil R
• Format: Article
• Language: English
• Subjects: antiplasmodial; malaria; sarganaphthoquinoic acid; sargaquinoic acid
• ISSN: 2305-6320; 2305-6320
• DOI: 10.3390/medicines6020047

Malaria continues to present a major health problem, especially in developing countries. The development of new antimalarial drugs to counter drug resistance and ensure a steady supply of new treatment options is therefore an important area of research. Meroditerpenes have previously been shown to exhibit antiplasmodial activity against a chloroquinone sensitive strain of (D10). In this study we explored the antiplasmodial activity of several semi-synthetic analogs of sargahydroquinoic acid. Sargahydroquinoic acid was isolated from the marine brown alga, and converted, semi-synthetically, to several analogs. The natural products, together with their synthetic derivatives were evaluated for their activity against the FCR-3 strain of as well as MDA-MB-231 breast cancer cells. Sarganaphthoquinoic acid and sargaquinoic acid showed the most promising antiplasmodial activity and low cytotoxicity. Synthetic modification of the natural product, sargahydroquinoic acid, resulted in the discovery of a highly selective antiplasmodial compound, sarganaphthoquinoic acid.