ADME study of drug candidates for the treatment of tuberculosis

• Grant number: 16/23229-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2017
• End date: February 28, 2019
• Field of knowledge: Health Sciences - Pharmacy
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Rosangela Gonçalves Peccinini
• Grantee: Taísa Busaranho Franchin
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis and responsible for 10.4 million of new cases in 2015. The treatment of tuberculosis consists of an association of Isoniazid, Rifampin, Pyrazinamide and Ethambutol. However, the cases of drug resistance have become very serious and worrying. Therefore, the research group of Unifesp-Diadema developed new compounds with potential antimycobacterial activity derived from pyrazinoic acid, the main metabolite of pyrazinamide that presented promising results. In the development of new drug candidates favorable pharmacokinetic properties represent a crucial decision point improving the chances of success. These results may be achieved early by using in vitro assays, which are used to predict pharmacokinetic as a screening method prior to in vivo study planning and design. The objective of this project is to perform the permeability characterization, using the Caco-2 monolayer model, and in vitro metabolism, using hepatic microsomes of rats and humans. Furthermore, physicochemical assays, through the evaluation of chemical and ex vivo stabilities and determination of log P by chromatographic method, are going to be performed. The obtained results will support decisions regarding the future of drug candidates and the planning of preclinical trials. (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)

FRANCHIN, TAISA BUSARANHO; ULIAN SILVA, BRUNA CRISTINA; DEGRANDIS, RONE APARECIDO; CORREA, MICHELLE FIDELIS; SIMOES DE QUEIROZ ARANHA, CECILIA MARIA; FERNANDES, JOAO PAULO S.; CAMPOS, MICHEL LEANDRO; PECCININI, ROSANGELA GONCALVES. Assessment of the Physicochemical Properties and Stability for Pharmacokinetic Prediction of Pyrazinoic Acid Derivatives. CURRENT DRUG METABOLISM, v. 21, n. 9, p. 714-721, 2020. (16/23139-2, 16/25028-3, 16/23229-1)

Academic Publications

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

FRANCHIN, Taísa Busaranho. ADME study of compounds derived from pyrazinoic acid with antimycobacterial activity. 2019. Master's Dissertation - Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara Araraquara.