N-Substituted 2-isonicotinoylhydrazinecarboxamides - new antimycobacterial active molecules

Rychtarčíková, Zuzana (author), Krátký, Martin (author), Gazvoda, Martin (author), Komlóová, Markéta (author), Polanc, Slovenko (author), Kočevar, Marijan (author), Stolařiková, Jiřina (author), Vinšová, Jarmila (author)

This report presents a new modification of the isoniazid (INH) structure linked with different anilines via a carbonyl group obtained by two synthetic procedures and with N-substituted 5-(pyridine-4-yl)-1,3,4-oxadiazole-2-amines prepared by their cyclisation. All synthesised derivatives were characterised by IR, NMR, MS and elemental analyses and were evaluated in vitro for their antimycobacterial activity against Mycobacterium tuberculosis H$_{37}$Rv, Mycobacterium avium 330/88, Mycobacterium kansasii 235/80 and one clinical isolated strain of M. kansasii 6509/96. 2-Isonicotinoyl-N-(4- octylphenyl)hydrazinecarboxamide displayed an in vitro efficacy comparable to that of INH for M. tuberculosis with minimum inhibitory concentrations (MICs) of 1–2 μM. Among the halogenated derivatives, the best anti-tuberculosis activity was found for 2-isonicotinoyl-N-(2,4,6-trichlorophenyl)hydrazinecarboxamide (MIC = 4 μM). In silico modelling on the enoyl-acyl carrier protein reductase InhA confirmed that longer alkyl substituents are advantageous for the interactions and affinity to InhA. Most of the hydrazinecarboxamides, especially those derived from 4-alkylanilines, exhibited significant activity against INH-resistant nontuberculous mycobacteria.

• Language: English
• Keywords: InhA inhibition, in silico docking, in vitro antimycobacterial activity, 2-isonicotinoylhydrazinecarboxamide, 5-(pyridine-4-yl)-1, 3, 4-oxadiazol-2-amine, tuberculosis
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2014
• Number of pages: Str. 3851-3868
• Numbering: Vol. 19, iss. 4
• PID: 20.500.12556/RUL-129216
• UDC: 547.86.057:615.2
• ISSN on article: 1420-3049
• DOI: 10.3390/molecules19043851
• COBISS.SI-ID: 1698863
• Publication date in RUL: 30.08.2021

Record is a part of a journal

• Title: Molecules
• Shortened title: Molecules
• Publisher: MDPI
• ISSN: 1420-3049
• COBISS.SI-ID: 18462981

Licences

• License: CC BY 3.0, Creative Commons Attribution 3.0 Unported
• Link: https://creativecommons.org/licenses/by/3.0/deed.en
• Description: You are free to reproduce and redistribute the material in any medium or format. You are free to remix, transform, and build upon the material for any purpose, even commercially. You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
• Licensing start date: 01.04.2014

Secondary language

• Language: Slovenian
• Keywords: medicina, organska kemija, farmakologija, tuberkuloza, zdravila za zdravljenje tuberkuloze, protibakterijska aktivnost, heterociklične spojine, derivati karboksamida, derivati hidrazina, INH