Integrated Evaluation of Pharmacokinetic and Biological Properties of Drug Candidates through Experimental and Computational Approaches

• Grant number: 25/10662-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2025
• End date: July 31, 2027
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Adriano Defini Andricopulo
• Grantee: Maynara Afonso
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID

Abstract

Neglected tropical diseases (NTDs) are a group of 21 diseases prevalent in tropical and subtropical regions, affecting over 1 billion people. Among this diverse group of diseases are Chagas disease and leishmaniasis, which stand out as two of the most important NTDs. Both are caused by kinetoplastid parasites and affect millions of people worldwide every year. Chemotherapeutic treatment options for leishmaniasis and Chagas disease are limited, with antimonials and nitroheterocycles causing significant side effects that often lead to treatment discontinuation. Also, the lack of new drugs and the prolonged use of existing ones have contributed to the emergence of resistant strains, highlighting the urgent need for the discovery of new therapeutic alternatives. Phenotypic approaches are commonly used for NTDs, as they are considered more successful in identifying new compound series compared to target-based screenings. Therefore, in this study, different compounds will be tested and characterized with the aim of identifying new candidates for the treatment of kinetoplastid diseases. Target identification can be a challenge for phenotypic screenings, although scientific advances have provided tools that can aid in the development and characterization of new drug candidates. Computational tools, such as molecular modeling and physicochemical properties prediction, will be used as they can be helpful by reducing costs and playing a fundamental role in rational drug design. Considering that appropriate pharmacokinetic profiles are critical for the success of drug candidates, assessing these parameters at early stages of development is of great importance. (AU)