Benzofuroxan Derivatives as Potent Agents against Multidrug-Resistant Mycobacterium tuberculosis

Author(s)

Fernandes, Guilherme F. S. ^{[1, 2]} ; Campos, Debora L. ^[1] ; Da Silva, Isabel C. ^[1] ; Prates, Joao L. B. ^{[1, 2]} ; Pavan, Aline R. ^{[1, 2]} ; Pavan, Fernando R. ^[1] ; Dos Santos, Jean L. ^{[1, 2]}

Affiliation

^[1] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Araraquara Jau Highway KM 01, BR-14800903 Araraquara, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Inst Chem, Francisco Degni St 55, BR-14800060 Araraquara, SP - Brazil

• Document type: Journal article
• Source: CHEMMEDCHEM; v. 16, n. 8 FEB 2021.
• Web of Science Citations: 0

Abstract

Tuberculosis (TB) is currently the leading cause of death related to infectious diseases worldwide, as reported by the World Health Organization. Moreover, the increasing number of multidrug-resistant tuberculosis (MDR-TB) cases has alarmed health agencies, warranting extensive efforts to discover novel drugs that are effective and also safe. In this study, 23 new compounds were synthesized and evaluated in vitro against the drug-resistant strains of M. tuberculosis. The compound 6-((3-fluoro-4-thiomorpholinophenyl)carbamoyl)benzo{[}c]{[}1,2,5]oxadiaz ole 1-N-oxide (5 b) was particularly remarkable in this regard as it demonstrated MIC90 values below 0.28 mu M against all the MDR strains evaluated, thus suggesting that this compound might have a different mechanism of action. Benzofuroxans are an attractive new class of anti-TB agents, exemplified by compound 5 b, with excellent potency against the replicating and drug-resistant strains of M. tuberculosis. (AU)

• FAPESP's process: 18/00163-0 - Development and search of new antimicrobials against Tuberculosis: from screening to pre-clinical studies in vivo
• Grantee: Fernando Rogério Pavan
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/17739-2 - Synthesis of New Nitroimidazooxazine Derivatives Designed as Antitubercular Agents
• Grantee: Guilherme Felipe dos Santos Fernandes
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 18/21778-3 - Analysis of in vitro, in vivo and mechanism of action of benzofuroxan compounds against Mycobacterium tuberculosis
• Grantee: Debora Leite Campos
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/24783-8 - Molecular toxicology testing of benzofuraxanes
• Grantee: Isabel Cristiane da Silva
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 18/11079-0 - Synthesis and antitubercular activity of new N-oxide compounds designed to treat multiresistant-tuberculosis
• Grantee: Jean Leandro dos Santos
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/09502-7 - Design, synthesis and antitubercular activity of new oxazolidinones useful for the treatment of multidrug-resistant tuberculosis
• Grantee: Guilherme Felipe dos Santos Fernandes
• Support Opportunities: Scholarships in Brazil - Doctorate