Next Article in Journal
Effect of Chum Salmon Egg Lectin on Tight Junctions in Caco-2 Cell Monolayers
Previous Article in Journal
Interference of Phenylethanoid Glycosides from Cistanche tubulosa with the MTT Assay
Article Menu

Export Article

Open AccessArticle
Molecules 2015, 20(5), 8072-8093; doi:10.3390/molecules20058072

Antimycobacterial and Anti-Inflammatory Activities of Substituted Chalcones Focusing on an Anti-Tuberculosis Dual Treatment Approach

1
Laboratório de Biologia do Reconhecer, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes 28013-602, RJ, Brazil
2
Laboratório de Produtos Bioativos, Curso de Farmácia, Universidade Federal do Rio de Janeiro, Campus Macaé, Pólo Novo Cavaleiro—IMMT, Macaé 27933-378, RJ, Brazil
3
Faculdade de Farmácia, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro 21941-901, RJ, Brazil
4
Instituto de Química, Universidade Federal Fluminense, Niterói, Rio de Janeiro 24020141, RJ, Brazil
5
Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, RJ, Brazil
E.B.L. and M.F.M. authors are joint senior authors on this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 28 February 2015 / Revised: 23 April 2015 / Accepted: 24 April 2015 / Published: 5 May 2015
(This article belongs to the Section Medicinal Chemistry)
View Full-Text   |   Download PDF [2145 KB, uploaded 5 May 2015]   |  

Abstract

Tuberculosis (TB) remains a serious public health problem aggravated by the emergence of M. tuberculosis (Mtb) strains resistant to multiple drugs (MDR). Delay in TB treatment, common in the MDR-TB cases, can lead to deleterious life-threatening inflammation in susceptible hyper-reactive individuals, encouraging the discovery of new anti-Mtb drugs and the use of adjunctive therapy based on anti-inflammatory interventions. In this study, a series of forty synthetic chalcones was evaluated in vitro for their anti-inflammatory and antimycobacterial properties and in silico for pharmacokinetic parameters. Seven compounds strongly inhibited NO and PGE2 production by LPS-stimulated macrophages through the specific inhibition of iNOS and COX-2 expression, respectively, with compounds 4 and 5 standing out in this respect. Four of the seven most active compounds were able to inhibit production of TNF-α and IL-1β. Chalcones that were not toxic to cultured macrophages were tested for antimycobacterial activity. Eight compounds were able to inhibit growth of the M. bovis BCG and Mtb H37Rv strains in bacterial cultures and in infected macrophages. Four of them, including compounds 4 and 5, were active against a hypervirulent clinical Mtb isolate as well. In silico analysis of ADMET properties showed that the evaluated chalcones displayed satisfactory pharmacokinetic parameters. In conclusion, the obtained data demonstrate that at least two of the studied chalcones, compounds 4 and 5, are promising antimycobacterial and anti-inflammatory agents, especially focusing on an anti-tuberculosis dual treatment approach. View Full-Text
Keywords: tuberculosis; Mycobacterium; inflammation; chalcone tuberculosis; Mycobacterium; inflammation; chalcone
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Ventura, T.L.B.; Calixto, S.D.; Abrahim-Vieira, B.A.; Souza, A.M.T.; Mello, M.V.P.; Rodrigues, C.R.; Miranda, L.S.M.; de Souza, R.O.M.A.; Leal, I.C.R.; Lasunskaia, E.B.; Muzitano, M.F. Antimycobacterial and Anti-Inflammatory Activities of Substituted Chalcones Focusing on an Anti-Tuberculosis Dual Treatment Approach. Molecules 2015, 20, 8072-8093.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top