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

Abstract

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.

Keywords

medicina;organska kemija;farmakologija;tuberkuloza;zdravila za zdravljenje tuberkuloze;protibakterijska aktivnost;heterociklične spojine;derivati karboksamida;derivati hidrazina;INH;InhA inhibition;in silico docking;in vitro antimycobacterial activity;2-isonicotinoylhydrazinecarboxamide;5-(pyridine-4-yl)-1,3,4-oxadiazol-2-amine;tuberculosis;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL FKKT - Faculty of Chemistry and Chemical Technology
UDC: 547.86.057:615.2
COBISS: 1698863 Link will open in a new window
ISSN: 1420-3049
Views: 231
Downloads: 67
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Other data

Secondary language: Slovenian
Secondary keywords: medicina;organska kemija;farmakologija;tuberkuloza;zdravila za zdravljenje tuberkuloze;protibakterijska aktivnost;heterociklične spojine;derivati karboksamida;derivati hidrazina;INH;
Type (COBISS): Article
Pages: str. 3851-3868
Volume: ǂVol. ǂ19
Issue: ǂno. ǂ4
Chronology: 2014
DOI: 10.3390/molecules19043851
ID: 13296243