Preparation and Biological Evaluation of Tuberculostatic-Chalcone Hybrids as Potential Agents against Tuberculosis

• Grant number: 15/09969-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2015
• End date: May 31, 2017
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Luis Octávio Regasini
• Grantee: Leticia Ribeiro de Assis
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

Tuberculostatics are crucial drugs for life expectancy, mainly to the HIV-positive patients. Several reasons justify the need for novel antimycobacterial agentes, including high mycobacterial resistance and high morbility and mortality related to tuberculosis. Thus, efforts are need to develop innovative tuberculostatic drugs. Chalcones are natural products belong to flavonoid class, and exhibit antimycobacterial activity. The current project proposes the preparation of two series of pyrazolines, which were designed by molecular hybridization. The design of the tuberculostatic-chalcone hybrids involved the condensation of chalconic subunit with pyrazine subunit (PZA-CHA) or quinolone subunit (NDX-CHA), from pyrazinamide and fluoroquinolones, tuberculostatic drugs of first and second lines, respectively. Hybrids will be prepared by reactions between pyrazinoic acid hydrazide or nalidixic acid hydrazide and chalcones subtituted by groups recommended by Topliss Manual Method (H, 4-Cl, 3,4-diCl, 4-OMe and 4-Me). Hybrids will be tested against sensible M. tuberculosis H37Rv strain (ATCC 27294). Compounds that demonstrated Minimum Inhibitory Concentration (MIC) equal or superior to 12.5 ug/mL, will be evaluated by cytotoxic activity assays, using kidney epitelial cells (Vero cells; ATCC CCL81) and murine macrophages (J774A.1; ATCC TIB-67). Selective index (SI) of hybrids will be calculated from IC50 values (half maximal inhibitory concentration to kill Vero cells or macrophages) and MIC values. SI = IC50/MIC. Compounds that showed SI values equal or superior to 10 will be submitted to inhibition of the intracelular forms of M. tuberculosis Erdman (ATCC 35801).

Academic Publications

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

ASSIS, Leticia Ribeiro de. Synthesis and biological evaluation of new tuberculostatic-chalcona hybrids as potential agents against tuberculosis. 2017. Master's Dissertation - Universidade Estadual Paulista (Unesp). Instituto de Biociências Letras e Ciências Exatas. São José do Rio Preto São José do Rio Preto.