Synthesis and biological evaluation of new tuberculostatic-chalcona hybrids as potential agents against tuberculosis

Author(s)

Leticia Ribeiro de Assis

• Document type: Master's Dissertation
• Press: São José do Rio Preto. 2017-06-21.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências Letras e Ciências Exatas. São José do Rio Preto
• Defense date: 2017-06-02
• Advisor: Luis Octavio Regasini; Fernando Rogério Pavan

Abstract

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB), wich is considered as a public health problem, due high number cases and deaths reported. Whereas a wide range of natural and synthetic chalconas (CHA) has presented activity against MTB, this study proposes the synthesis of new tuberculostatic-chalcone as molecular hybrids against MTB. Molecular hybrids were obtained in three stages: i) synthesis of chalcones; ii) synthesis of pirazinoic (PZA) and nalidixic (NDX) acid hydrazides; iii) synthesis of molecular pirazinamide-chalcone (PZA-CHA, serie I) and nalidixic acid-chalcone (NDX-CHA, serie II) hydrids. From reaction between chalcones and pirazinoic and nalidixic acid hydrazides were synthesized 26 new N-acylhydrazones. Among these, 13 from serie I and 13 from serie II with yields ranging from 4 to 63%. N-acylhydrazones were evaluated against Mycobacterium tuberculosis H37Rv ATCC 27294 strain. Among 26 evaluated molecular hybrids, para-methylated on ring B hybrid 61A (serie II) displayed potent activity against MTB at minimal inhibitory concentration of 37.1 µmol/L, evidencing hybridization molecular was efficient for anti-MTB chemical entity production. (AU)

• FAPESP's process: 15/09969-0 - Preparation and Biological Evaluation of Tuberculostatic-Chalcone Hybrids as Potential Agents against Tuberculosis
• Grantee: Leticia Ribeiro de Assis
• Support Opportunities: Scholarships in Brazil - Master