Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Design, Synthesis, and Characterization of N-Oxide-Containing Heterocycles with in Vivo Sterilizing Antitubercular Activity

Full text
Author(s):
Show less -
dos Santos Fernandes, Guilherme Felipe [1, 2, 3] ; de Souza, Paula Carolina [1, 4] ; Moreno-Viguri, Elsa [2] ; Santivanez-Veliz, Mery [2] ; Paucar, Rocio [2] ; Perez-Silanes, Silvia [2] ; Chegaev, Konstantin [5] ; Guglielmo, Stefano [5] ; Lazzarato, Loretta [5] ; Fruttero, Roberta [5] ; Chin, Chung Man [1] ; da Silva, Patricia Bento ; Chorilli, Marlus [1] ; Solcia, Mariana Cristina [1] ; Ribeiro, Camila Maringolo [1] ; Paiva Silva, Caio Sander [1] ; Marino, Leonardo Biancolino [1] ; Bosquesi, Priscila Longhin [1] ; Hunt, Debbie M. [6] ; de Carvalho, Luiz Pedro S. [6] ; de Souza Costa, Carlos Alberto [7] ; Cho, Sang Hyun [4] ; Wang, Yuehong [4] ; Franzblau, Scott Gary [4] ; Pavan, Fernando Rogerio [1] ; dos Santos, Jean Leandro [1, 3]
Total Authors: 26
Affiliation:
[1] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, BR-14800903 Araraquara - Brazil
[2] Univ Navarra, Dept Organ & Pharmaceut Chem, Inst Salud Trop, Pamplona 31008 - Spain
[3] Sao Paulo State Univ UNESP, Inst Chem, BR-14800060 Araraquara - Brazil
[4] Univ Illinois, Inst TB Res, Chicago, IL 60607 - USA
[5] Univ Turin, Dipartimento Sci & Tecnol Farm, I-10124 Turin - Italy
[6] Francis Crick Inst, Mycobacterial Metab & Antibiot Res Lab, 1 Midland Rd, London NW1 1AT - England
[7] Sao Paulo State Univ UNESP, Sch Odontol, BR-14801903 Araraquara - Brazil
Total Affiliations: 7
Document type: Journal article
Source: Journal of Medicinal Chemistry; v. 60, n. 20, p. 8647-8660, OCT 26 2017.
Web of Science Citations: 10
Abstract

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is the infectious disease responsible for the highest number of deaths worldwide. Herein, 22 new N-oxide-containing compounds were synthesized followed by in vitro and in vivo evaluation of their antitubercular potential against Mtb. Compound 8 was found to be the most promising compound, with MIC(90)values of 1.10 and 6.62 mu M against active and nonreplicating Mtb, respectively. Additionally, we carried out in vivo experiments to confirm the safety and efficacy of compound 8; the compound was found to be orally bioavailable and highly effective, leading to a reduction of Mtb to undetectable levels in a mouse model of infection. Microarray-based initial studies on the mechanism of action suggest that compound 8 blocks translation. Altogether, these results indicate that benzofuroxan derivative 8 is a promising lead compound for the, development of a novel chemical class of antitubercular drugs. (AU)

FAPESP's process: 15/19531-1 - Targeting histone deacetylase (HDAC-1 and HDAC-2) as mechanisms to induce fetal hemoglobin in sickle cell disease
Grantee:Jean Leandro dos Santos
Support Opportunities: Regular Research Grants
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 Opportunities: Research Grants - Young Investigators Grants
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 Opportunities: 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 Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 14/03920-6 - Evaluation of pharmacological interaction and bactericidal kinetics of new furoxanic molecules in combination with rifampicin, isoniazid, amikacin, and moxifloxacin against Mycobacterium tuberculosis H37Rv
Grantee:Camila Maríngolo Ribeiro
Support Opportunities: Scholarships in Brazil - Scientific Initiation
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
FAPESP's process: 16/02860-5 - In vitro and in vivo studies of furoxan compounds: permeability, frequency of resistance, activity against resistance strains and in vivo efficacy
Grantee:Paula Carolina de Souza
Support Opportunities: Scholarships abroad - Research Internship - Doctorate
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 Opportunities: Scholarships in Brazil - Master