Naphthoquinone Derivatives as Scaffold to Develop New Drugs for Tuberculosis Treatment
Despite being a curable disease, tuberculosis (TB) remains a public health problem worldwide mainly due to lengthy treatment, as well as its toxic effects, TB/HIV co-infection and the emergence of resistant strains. These barriers reinforcing the need for development of new antimicrobial agents, tha...
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Published in | Frontiers in microbiology Vol. 9; p. 673 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
09.04.2018
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Subjects | |
Online Access | Get full text |
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Summary: | Despite being a curable disease, tuberculosis (TB) remains a public health problem worldwide mainly due to lengthy treatment, as well as its toxic effects, TB/HIV co-infection and the emergence of resistant
strains. These barriers reinforcing the need for development of new antimicrobial agents, that ideally should reduce the time of treatment and be active against susceptible and resistant strains. Quinones are compounds found in natural sources and among them, the naphthoquinones show antifungal, antiparasitic, and antimycobacterial activity. Thus, we evaluated the potential antimycobacterial activity of six 1,4-naphthoquinones derivatives. We determined the minimum inhibitory concentration (MIC) of the compounds against three
strains: a pan-susceptible H37Rv (ATCC 27294); one mono-resistant to isoniazid (ATCC 35822); and one mono-resistant to rifampicin (ATCC 35838); the cytotoxicity in the J774A.1 (ATCC TIB-67) macrophage lineage; performed
analysis about absorption, distribution, metabolism, and excretion (ADME) and docking sites. All evaluated naphthoquinones were active against the three strains with MIC between 206.6 and 12.5 μM, and the compounds with lower MIC values have also showed low cytotoxicity. Moreover, two naphthoquinones derivatives 5 and 6 probably do not exhibit cross resistance with isoniazid and rifampicin, respectively, and regarding ADME analysis, no compound violated the Lipinski's rule-of-five. Considering the set of findings in this study, we conclude that these naphthoquinones could be promising scaffolds to develop new therapeutic strategies to TB. |
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Bibliography: | Reviewed by: Katiany Rizzieri Caleffi Ferracioli, Universidade Estadual de Maringá, Brazil; Sandeep Sharma, University of Pennsylvania, United States; Banasri Hazra, Jadavpur University, India Edited by: Fernando Rogerio Pavan, Universidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP), Brazil This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology |
ISSN: | 1664-302X 1664-302X |
DOI: | 10.3389/fmicb.2018.00673 |