Development and parallel microscale synthesis of heterocyclic compounds using fragment-based drug design (FBDD) as potential agents against Leishmania braziliensis

• Grant number: 24/22535-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2025
• End date: February 28, 2027
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Daniel Gedder Silva
• Grantee: Ahmad Abubakar
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 23/11804-5 - Combining Microscale Parallel Synthesis (MPS) and Medium-Throughput Screening (MTS) for Accelerated Hit-to-lead Optimization of Anti-Infective Agents., AP.JP

Abstract

Leishmaniasis belongs to a group of neglected tropical infectious diseases, characterized by low research investment and lack of interest from the pharmaceutical industry. These diseases are generally endemic in Global South countries, affecting low-income populations. In an attempt to mitigate the harm caused by the disease and the lack of promising treatments, fragment-based drug design (FBDD) emerges as an excellent alternative. A "fragment" is a chemically less complex compound and does not possess all the necessary characteristics of a drug but can serve as a starting point for optimization as a leishmanicidal agent. The "rule of three" for fragment development facilitates the selection of less structurally complex chemical compounds. With this strategy, database searches in ChEMBL revealed that indazole-based fragments have potential against leishmaniasis. Aiming to synthesize indazole derivatives through parallel microscale synthesis, synthetic routes will be explored to modify different positions of the nucleus under study. Following the synthesis, biological assays will be conducted against Leishmania braziliensis to study the structure-activity relationship (SAR). Fragment-growing techniques will be applied to obtain promising compounds for the treatment of infections caused by this parasite.