Design and synthesis of readthrough compounds

• Grant number: 17/02093-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: July 05, 2017
• End date: July 04, 2018
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Júlio Cezar Pastre
• Grantee: Mariana Celestina Frojuello Costa Bernstorff Damião
• Supervisor: Alan P. Kozikowski
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of Illinois at Chicago (UIC), United States
• Associated to the scholarship: 15/18572-6 - Continuous flow synthesis of 3-thio-1,2,4-triazoles and biological evaluation, BP.DR

Abstract

Chemical-induced "readthrough" of premature termination codons is an interesting approach to be explored by medicinal chemists for the treatment of genetic disorders caused by nonsense mutations. In an effort to develop new "readthrough" molecules, we intend to optimize pharmacodynamics and ADMET properties of previously synthesized analogs, and to design and generate new compounds based on the structure of the "readthrough" molecule GJ072. The compounds will be evaluated by cell fluorescence microscopy, and SAR studies will be performed, in order to make predictions as to how certain structural changes might alter the biological results. We aim to design and synthesize a variety of compounds with enhanced drug-like properties that might represent an alternative for the treatment of nonsense-mediated disorders. (AU)