Kamdem, B.P.; Boyom, F.F. Inhibitors of Farnesyl Diphosphate Synthase and Squalene Synthase: Potential Source for Anti-Trypanosomatidae Drug Discovery. Drugs Drug Candidates2023, 2, 624-652.
Kamdem, B.P.; Boyom, F.F. Inhibitors of Farnesyl Diphosphate Synthase and Squalene Synthase: Potential Source for Anti-Trypanosomatidae Drug Discovery. Drugs Drug Candidates 2023, 2, 624-652.
Kamdem, B.P.; Boyom, F.F. Inhibitors of Farnesyl Diphosphate Synthase and Squalene Synthase: Potential Source for Anti-Trypanosomatidae Drug Discovery. Drugs Drug Candidates2023, 2, 624-652.
Kamdem, B.P.; Boyom, F.F. Inhibitors of Farnesyl Diphosphate Synthase and Squalene Synthase: Potential Source for Anti-Trypanosomatidae Drug Discovery. Drugs Drug Candidates 2023, 2, 624-652.
Abstract
Trypanosomatids are mainly responsible for leishmaniasis, sleeping sickness, and Chagas disease, which are the most challenging among the neglected tropical diseases due to the problem of drug resistance. Although problems of target deconvolution and polypharmacology are encountered, a target-based approach is a rational method for screening drug candidates targeting a biomolecule that causes diseases. The present study aims to summarize the latest information re-garding potential inhibitors of squalene synthase and farnesyl phosphate synthase with anti-Trypanosomatidae activity. The information was obtained by referencing textbooks and major scientific databases from their inception until April 2023. Based on in vitro experiments, more than seventy compounds were reported to inhibit squalene synthase and farnesyl diphosphate synthase. Among these compounds, more than 30 were found to be active in vitro against Trypanosomatidae, inferring that these compounds can be prospected as scaffolds for the development of new drugs against trypanosomatid-related infections. Over-all, natural and synthetic products can inhibit enzymes that are crucial for the survival and virulence of trypanosomatids. Moreover, in vitro experiments have confirmed the activity of more than half of these inhibitors using cell-based as-says. Nevertheless, additional studies on the cytotoxicity, pharmacokinetics, and lead optimization of potent anti-Trypanosomatid compounds should be investi-gated.
Medicine and Pharmacology, Pharmacology and Toxicology
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