Pharmacokinetic Evaluation of a Novel Synthesis Anti-malarial Compound

[Speaker] Pravin Kendrekar:1
[Co-author] Samson Mashele:1, Deepak Salunke:2
1:Central University of Technology, South Africa, 2:Department of Chemistry & Centre for Advanced Studies in Chemistry, Punjab University, Chandigarh, India

Malaria is a global health problem that causes significant mortality and morbidity, with more than 1million deaths per year caused by Plasmodium falciparum. Most antimalarial drugs face decreased efficacy due to the emergence of resistant parasites, which necessitates the discovery of new drugs. Artemisinin-based combination therapy (ACT) is recommended as first-line treatment for uncomplicated Plasmodium falciparum malaria and has significantly reduced the malaria burden in most endemic countries, but the emergence of artemisinin-resistant malaria parasites in Cambodia, Myanmar, Thailand and Vietnam underscores the importance and urgency to push the discovery and development of new effective anti-malarial drugs to its highest level. Thus to achieve this goal, the unit of drug discovery research at central university of technology (CUT), Bloemfontein, South Africa has synthesized a library of novel amino-alkylated chalcones and analogues by means of the mannich reaction. The compounds were evaluated for their in vitro anti-malarial activity against chloroquine-sensitive (D10) and chloroquine-resistant (K1) P. falciparum strains, and cytotoxicity against Chinese Hamster Ovarian (CHO) cells by MTT assays. The most promising compound shows 25% bioavailability, we are busy for the further study with artemisinin-resistant and isolated malaria parasites from South-East Asia.
Methods: Pharmacokinetic studies were conducted for GPK-102 in C57/BL6 mice. GPK-102 was administered at a dose of 5 mg/kg intravenously or 15 mg/kg orally. Blood samples were collected by means of tail bleeding at pre-determined time intervals. Drug concentrations were determined with a LC/MS/MS method

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