Last Updated: 06/11/2023
Identification of new antimalarial compounds for target-centered drug repositioning approach
Objectives
*Original title in Portuguese: Identificação de novos tratamentos antimaláricos através de uma abordagem de “reposicionamento de fármacos” centrada no alvo
To evaluate new compounds for antimalarial activity for asexual blood stages and cytotoxicity and perform a “de novo” study to identify transmission-blocking compounds against proteins that are overexpressed at the sporozoite stage and proteins that are differentially expressed in gametocytes.
Malaria is an infectious disease caused by protozoa of the genus Plasmodium. The emergence of Plasmodium resistance to the most antimalarial drugs has highlighted the urgency of identifying and clarifying the mechanisms of new antimalarial drugs. However, the development of a new drug is a long and expensive. “Drug Repositioning” is the application of known and approved compounds that are redirected to new uses outside the scope of the original medical indication and represents the fastest way to get a drug because it is readily available for clinical trials. Recently, epirubicin was identified and this molecule showed optimal activity against the asexual stage of Plasmodium in both in vitro inhibition assays and in vivo efficacy assays. However, its toxicity precludes the use for malaria treatment. Therefore, this study intends to use the epirubicin scaffold to identify new molecules with less toxicity and/or greater activity against malaria parasites. A preliminary search on the MolPort website identified ~ 50 commercially available compounds with similarity above 80% (Tanimoto coefficient) to epirubicin. Drugs thus identified will be evaluated in vivo for their ability to block the development of the parasite in the hepatic phase or its sporozoite development.
Jun 2020 — Aug 2021
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