Development of novel series of potent and selective heterocyclic compounds as anti-infectives agents

• Grant number: 21/11899-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: January 30, 2022
• End date: January 29, 2023
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Flavio da Silva Emery
• Grantee: Daniel Gedder Silva
• Supervisor: Matthew H. Todd
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University College London (UCL), England
• Associated to the scholarship: 17/22001-0 - Synthesis and evaluation of new heterocyclic compounds as potential antitrypanosomal agents, BP.PD

Abstract

A series of new heterocyclic compounds will be synthesized and tested against both a parasitic panel and MRSA and for cytotoxicity. Knowledge of the molecular target of these phenotypically active compounds will be obtained which will facilitate the next phase of the drug discovery process: target (structure)-based projects against better validated targets, accelerating the subsequent optimization of late lead compounds. A target-based approach can be used to circumvent pharmacokinetic or toxicological issues using techniques such as scaffold hopping. In order to achieve these goals, we will design and synthesize a new series of heterocyclic compounds with improved calculated pharmacokinetics properties that explore chemical space inaccessible to the current approaches. All compounds will be evaluated in growth inhibition assays and the stability of selected compounds will be investigated with mouse microsomes, solubility and protein binding assays and, ultimately, in vivo efficacy studies. These results will allow us to select the most promising compound for future translational work towards much-needed new therapies for infectious diseases. Strikingly, all the data in the project will be made publicly available in real-time, allowing others to contribute to the research as it proceeds: this "open science" approach maximizes the impact of the funded research. (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)

DICHIARA, MARIA; SIMPSON, QUILLON J.; QUOTADAMO, ANTONIO; JALANI, HITESH B.; HUANG, ANSON X.; MILLARD, CAROLINE C.; KLUG, DANA M.; TSE, EDWIN G.; TODD, MATTHEW H.; SILVA, DANIEL GEDDER; et al. Structure-Property Optimization of a Series of Imidazopyridines for Visceral Leishmaniasis. ACS INFECTIOUS DISEASES, v. 9, n. 8, p. 18-pg., 2023-07-07. (21/11899-0, 17/21146-4)