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

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

Abstract

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)

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, 2020-10-05. (19/03018-4, 17/21154-7, 18/10359-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SANCHES, Luccas Missfeldt. Antimalarial potentially active against resistance: design and synthesis of dendrons and dendrimers directed to infected erythrocytes. 2023. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.