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Benzo[ a ]phenazine derivatives: Promising scaffolds to combat resistant Mycobacterium tuberculosis
Author(s) -
Halicki Priscila Cristina Bartolomeu,
Silva Eufrânio Nunes,
Jardim Guilherme Augusto de Melo,
Almeida Renata Gomes de,
Vicenti Juliano Rosa de Menezes,
Gonçalves Bruna Lisboa,
Silva Pedro Eduardo Almeida,
Ramos Daniela Fernandes
Publication year - 2021
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13853
Subject(s) - phenazine , mycobacterium tuberculosis , antimycobacterial , rifampicin , antimicrobial , cytotoxicity , microbiology and biotechnology , tuberculosis , chemistry , multiple drug resistance , mycobacterium , mechanism of action , minimum inhibitory concentration , antibiotics , in vivo , biology , in vitro , medicine , biochemistry , pathology
The continuous emergence of resistant Mycobacterium tuberculosis keeps tuberculosis (TB) treatment options still insufficient, and new therapeutic alternatives are urgently needed. Considering the antimycobacterial activity of phenazine derivatives previously reported by our research group, we aimed to explore possible applications to circumvent the resistance in M. tuberculosis . Firstly, we evaluated the antimicrobial activity of seven benzo[ a ]phenazine derivatives against eleven M. tuberculosis strains: ten resistant and one susceptible (H 37 Rv). Then, we determined the cytotoxicity of benzo[ a ]phenazine derivatives and investigated the possible mechanism of action of the most promising compound. Among them, compound 10 was the only one active against all strains evaluated, with a minimum inhibitory concentration between 18.3 and 146.5 µM. For some resistant strains, this compound showed antimicrobial activity higher than rifampicin and it was also active against MDR strains, indicating an absence of cross‐resistance with anti‐TB drugs. Also, 10 showed a pharmacological safety for further in vivo studies and its mechanism of action seems to be related to oxidative stress. Thus, our findings indicate that benzo[ a ]phenazine derivatives are promising scaffolds for the development of new anti‐TB drugs, mainly focusing on the treatment of resistant TB cases.