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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Synthesis and biological activity of furoxan derivatives against Mycobacterium tuberculosis

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dos Santos Fernandes, Guilherme Felipe ; de Souza, Paula Carolina ; Marino, Leonardo Biancolino ; Chegaev, Konstantin ; Guglielmo, Stefano ; Lazzarato, Loretta ; Fruttero, Roberta ; Chung, Man Chin ; Pavan, Fernando Rogerio ; dos Santos, Jean Leandro
Total Authors: 10
Document type: Journal article
Source: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 123, p. 523-531, NOV 10 2016.
Web of Science Citations: 22

Tuberculosis (TB) remains a serious health problem responsible to cause millions of deaths annually. The scenario becomes alarming when it is evaluated that the number of new drugs does not increase proportionally to the emergence of resistance to the current therapy. Furoxan derivatives, known as nitric oxide (NO) donors, have been described to exhibit antitubercular activity. Herein, a novel series of hybrid furoxan derivatives (1,2,5-oxadiazole 2-N-oxide) (compounds 4a-c, 8a-c and 14a-c) were designed, synthesized and evaluated in vitro against Mycobacterium tuberculosis (MTh) H(37)Rv (ATCC 27294) and a clinical isolate MDR-TB strain. The furoxan derivatives have exhibited MIC90 values ranging from 1.03 to 62 mu M (H(37)Rv) and 7.0-50.0 mu M (MDR-TB). For the most active compounds (8c, 14a, 14b and 14c) the selectivity index ranged from 3.78 to 52.74 (MRC-5 cells) and 1.25-34.78 (J774A.1 cells). In addition, it was characterized for those compounds logP(o/w), values between 2.1 and 2.9. All compounds were able to release NO at levels ranging from 0.16 to 44.23%. Among the series, the phenylsulfonyl furoxan derivatives (compounds 14a-c) were the best NO-donor with the lowest MIC90 values. The most active compound (14c) was also stable at different pHs (5.0 and 7.4). In conclusion, furoxan derivatives were identified as new promising compounds useful to treat tuberculosis. (C) 2016 Elsevier Masson SAS. All rights reserved. (AU)

FAPESP's process: 13/14957-5 - Research potential against tuberculosis of a new class of furoxan compounds and nanostructured compounds of the ruthenium(II) and copper (II)
Grantee:Fernando Rogério Pavan
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 14/02240-1 - Design, Synthesis and anti Mycobacterium tuberculosis activity of new N-oxides derivatives
Grantee:Guilherme Felipe dos Santos Fernandes
Support type: Scholarships in Brazil - Master
FAPESP's process: 14/24811-0 - Design and synthesis of new 1,4-di-N-oxide quinoxaline as antitubercular compounds to treat multi drug-resistant (MDR) and latent tuberculosis
Grantee:Guilherme Felipe dos Santos Fernandes
Support type: Scholarships abroad - Research Internship - Master's degree
FAPESP's process: 14/11586-9 - Studies in vitro and in vivo of furoxan compounds with potential application for the treatment of tuberculosis
Grantee:Paula Carolina de Souza
Support type: Scholarships in Brazil - Doctorate