In vitro tests of phosphopantetheine adenililtrasferase inhibitors potentially active against Mycobacterium tuberculosis and design of novel compounds

• Grant number: 15/21470-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: June 06, 2016
• End date: June 05, 2017
• Field of knowledge: Physical Sciences and Mathematics - Chemistry
• Principal Investigator: Elizabeth Igne Ferreira
• Grantee: Marina Candido Primi
• Supervisor: Scott Franzblau
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Illinois at Chicago (UIC), United States
• Associated to the scholarship: 13/15947-3 - New antituberculosis agents candidates: design and synthesis of phosphopantetheine adenylyltransferase inhibitors, BP.DR

Abstract

The purpose of this project is to complement the PhD project entitled 'New tuberculostatic drug candidates: design, synthesis and biological activity of phosphopantetheine adenililtrasferase inhibitors'. In this project, we are studying the enzyme phosphopantetheine adenililtrasferase (PPAT) as a new target in the search for selective inhibitors towards anti-tuberculosis (TB) drug candidates. Finding new drug leads with novel mechanisms of action to overcome drug resistant TB is of utmost importance. In this sense, PPAT has been triggering the scientific research community interest nowadays since it displays a regulatory role in the M. tuberculosis coenzyme A (CoA) biosynthesis. Potential PPAT inhibitors were designed through Structure-Based Drug Design and Ligand-Based Drug Design approaches. Docking simulations were performed with the 78 potential inhibitors previously designed and then, the most promising ones were selected to be synthesized and to have their biological activity evaluated. Microbiological in vitro tests of these compounds will allow further design, synthesis and biological evaluation of novel optimized compounds. The Institute for Tuberculosis Research (ITR) is the unique center for tuberculosis in the world that brings an industrial model of drug discovery into an academic environment. Beside this, ITR has all the necessary facilities to perform microbiological in vitro tests of the proposed compounds, as well as to design and synthesize novel potential enzyme inhibitors. (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)

PRIMI, MARINA C.; TAVARES, MAURICIO T.; KLEIN, LARRY L.; IZARD, TINA; SANT'ANNA, CARLOS M. R.; FRANZBLAU, SCOTT G.; FERREIRA, I, ELIZABETH. Design of Novel Phosphopantetheine Adenylyltransferase Inhibitors: A Potential New Approach to Tackle Mycobacterium tuberculosis. CURRENT TOPICS IN MEDICINAL CHEMISTRY, v. 21, n. 13, p. 1186-1197, 2021. (13/15947-3, 15/21470-0)