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 H37Rv, 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.

• MeSH
• Amines chemistry   MeSH
• Aniline Compounds chemistry   MeSH
• Antitubercular Agents chemical synthesis   pharmacology   MeSH
• Mycobacterium Infections, Nontuberculous microbiology   MeSH
• Azoles chemistry   MeSH
• Drug Resistance, Bacterial MeSH
• Bacterial Proteins antagonists & inhibitors   chemistry   MeSH
• Cyclization MeSH
• Isoniazid analogs & derivatives   chemical synthesis   pharmacology   MeSH
• Humans MeSH
• Microbial Sensitivity Tests MeSH
• Mycobacterium avium drug effects   enzymology   growth & development   MeSH
• Mycobacterium kansasii drug effects   enzymology   growth & development   isolation & purification   MeSH
• Mycobacterium tuberculosis drug effects   enzymology   growth & development   MeSH
• Oxidoreductases antagonists & inhibitors   chemistry   MeSH
• Pyridines chemistry   MeSH
• Molecular Docking Simulation MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Amines MeSH
• aniline MeSH Browser
• Aniline Compounds MeSH
• Antitubercular Agents MeSH
• Azoles MeSH
• Bacterial Proteins MeSH
• InhA protein, Mycobacterium MeSH Browser
• Isoniazid MeSH
• Oxidoreductases MeSH
• Pyridines MeSH