BIOCONJUGATION OF ANTIMICROBIAL PEPTIDES WITH ORGANOMETALLICS COMPOUNDS AS A THERAPEUTIC OPTION FOR LEISHMANIASIS

• Grant number: 24/14185-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2025
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Eduardo Maffud Cilli
• Grantee: Fernanda Vitória Araújo Silva
• Host Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Neglected diseases, in general, are those that affect marginalized populations in isolated areas, especially in Latin America. These diseases are a consequence of an unequal development process that determines populations in extreme poverty, generating high risks of morbidity for individuals subjected to these conditions of precarious sanitary structure, inadequate nutrition, and difficulties in accessing health services. In epidemiological aspects, some infectious diseases caused by protozoa are increasingly out of control, as is the case of leishmaniasis, caused by protozoa belonging to the Trypanosomatidae family and Leishmania genus. Although, according to the Pan American Health Organization (PAHO), in the last 20 years, 1,067,759 cases of cutaneous and mucosal leishmaniasis have been reported, currently available therapeutic options are limited, often ineffective and potentially toxic. Therefore, there is a need to fill this gap, searching for new therapeutic alternatives that perform more precisely. Consequently, the fundamental objective of the project is to produce a treatment for Leishmaniasis from the bioconjugation of antimicrobial peptides functionalized with organometallic groups. To achieve this, antimicrobial peptides will be coupled to ferrocene with anti-parasitic activity, aiming to increase the selectivity and potency of the conjugates obtained. Preliminary results indicate that the bioconjugates produced have a more concrete action against parasites and are more selective in relation to host cells, which shows the potential of the bioconjugation technique to reduce the toxicity of compounds to the host compared to the control drug Amphotericin B (Anf B). This suggests a significant contribution to the development of new drugs to treat cutaneous and visceral leishmaniasis, which are the main focuses of this study.