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Potentially active antimalarials against resistance: planning and synthesis of dendrons and dendrimers targeting infected erythrocytes

Grant number: 18/10359-0
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): October 01, 2018
Effective date (End): April 17, 2023
Field of knowledge:Health Sciences - Pharmacy
Principal researcher:Elizabeth Igne Ferreira
Grantee:Luccas Missfeldt Sanches
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Malaria is a potentially fatal disease caused by protozoa of the Plasmodium genus and it affects human erythrocytes. In several regions of the world, reports of the emergence of parasites resistant to the main drugs in use have been made, leading to a rise in disease mortality rate. Artemisinin Combination Therapies (ACTs) are strongly recommended by the World Health Organization for the treatment of Malaria, including resistance cases. Heparin and its derivatives are able to bind to infected erythrocytes, making them viable, which may allow its use for drug targeting. Latentiation is the term used for drug derivatives that release the original drug after suffering enzymatic activity. The technique can be used to bind drugs to carrier molecules and the covalent bond is broken during biotransformation processes, which releases the active molecule and may be used to increase its concentration in affected regions and cause a precise pathogen intervention. Dendrimers are viable carriers due to its biological barriers passing ability. Therapies that combine drugs with different mechanisms of action, such as ACTs, is an an option to reduce the emergence of drug resistance by Plasmodium species. Therefore, the current work aims to synthesize dendrimers targeted by heparin derivatives and carrying mefloquine and artesunate (an ACT), which could increase therapeutic efficacy and aid the deterrent of Plasmodium drug resistance emergence. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RENAN VINICIUS DE ARAÚJO; SORAYA SILVA SANTOS; LUCCAS MISSFELDT SANCHES; JEANINE GIAROLLA; OMAR EL SEOUD; ELIZABETH IGNE FERREIRA. Malaria and tuberculosis as diseases of neglected populations: state of the art in chemotherapy and advances in the search for new drugs. Memórias do Instituto Oswaldo Cruz, v. 115, . (18/10359-0, 17/21154-7, 19/03018-4)

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