Next Article in Journal
Identification of Polar Constituents in the Decoction of Juglans mandshurica and in the Medicated Egg Prepared with the Decoction by HPLC-Q-TOF MS2
Previous Article in Journal
Origin and Formation Mechanism Investigation of Compound Precipitation from the Traditional Chinese Prescription Huang-Lian-Jie-Du-Tang by Isothermal Titration Calorimetry
Article Menu
Issue 9 (September) cover image

Export Article

Open AccessArticle
Molecules 2017, 22(9), 1457;

Mechanochemical Synthesis and Biological Evaluation of Novel Isoniazid Derivatives with Potent Antitubercular Activity

Department of Process Engineering, Université de Toulouse, Mines-Albi, CNRS UMR 5302, Centre RAPSODEE, Campus Jarlard, 81013 Albi, France
Department of Chemistry, Université de Toulouse, UPS, CNRS UMR 5068, LSPCMIB, 118 Route de Narbonne, 31062 Toulouse, France
CNRS, Laboratoire de Synthèse et Physico-Chimie de Molécules d’Intérêt Biologique, LSPCMIB, UMR-5068, 118 Route de Narbonne, 31062 Toulouse, France
Department of Biochemistry, Comenius University in Bratislava, Faculty of Natural Sciences, Mlynská Dolina, Ilkovičova 6, 84215 Bratislava, Slovakia
Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia; via Ferrata 1, 27100 Pavia, Italy
Current address: Université de Lille, UMET, Unité Matériaux et Transformations, CNRS UMR 8207, F-59000 Lille, France.
Authors to whom correspondence should be addressed.
Received: 2 July 2017 / Revised: 19 July 2017 / Accepted: 24 July 2017 / Published: 1 September 2017
(This article belongs to the Section Medicinal Chemistry)
Full-Text   |   PDF [9621 KB, uploaded 4 September 2017]   |  


A series of isoniazid derivatives bearing a phenolic or heteroaromatic coupled frame were obtained by mechanochemical means. Their pH stability and their structural (conformer/isomer) analysis were checked. The activity of prepared derivatives against Mycobacterium tuberculosis cell growth was evaluated. Some compounds such as phenolic hydrazine 1a and almost all heteroaromatic ones, especially 2, 5 and 7, are more active than isoniazid, and their activity against some M. tuberculosis MDR clinical isolates was determined. Compounds 1a and 7 present a selectivity index >1400 evaluated on MRC5 human fibroblast cells. The mechanism of action of selected hydrazones was demonstrated to block mycolic acid synthesis due to InhA inhibition inside the mycobacterial cell. View Full-Text
Keywords: Mycobacterium tuberculosis; mechanochemistry; hydrazone Mycobacterium tuberculosis; mechanochemistry; hydrazone

Graphical abstract

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).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Oliveira, P.F.M.; Guidetti, B.; Chamayou, A.; André-Barrès, C.; Madacki, J.; Korduláková, J.; Mori, G.; Orena, B.S.; Chiarelli, L.R.; Pasca, M.R.; Lherbet, C.; Carayon, C.; Massou, S.; Baron, M.; Baltas, M. Mechanochemical Synthesis and Biological Evaluation of Novel Isoniazid Derivatives with Potent Antitubercular Activity. Molecules 2017, 22, 1457.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



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