20.500.12556/RUL-129216 N-Substituted 2-isonicotinoylhydrazinecarboxamides - new antimycobacterial active molecules 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. InhA inhibition in silico docking in vitro antimycobacterial activity 2-isonicotinoylhydrazinecarboxamide 5-(pyridine-4-yl)-1 3 4-oxadiazol-2-amine tuberculosis medicina organska kemija farmakologija tuberkuloza zdravila za zdravljenje tuberkuloze protibakterijska aktivnost heterociklične spojine derivati karboksamida derivati hidrazina INH true false true Angleški jezik Slovenski jezik Članek v reviji 2021-08-30 11:47:12 2021-08-30 11:47:13 2022-09-08 04:07:18 0000-00-00 00:00:00 2014 0 0 Str. 3851-3868 iss. 4 Vol. 19 2014 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 547.86.057:615.2 1420-3049 10.3390/molecules19043851 1698863 RAZ_Rychtarcikova_Zuzana_2014.pdf RAZ_Rychtarcikova_Zuzana_2014.pdf 1 7457F4C704AEBC50B23007433FD7337B 36b0115a6ac1f43dae1b6ad558e1ee5eeb2c99c602aad15a3799aa85157c32f2 8b6bfe4a-0977-11ec-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=146168 http://www.mdpi.com/1420-3049/19/4/3851 1 0c79243d-0977-11ec-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=146167 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0