N-Substituted 2-isonicotinoylhydrazinecarboxamides - new antimycobacterial active molecules

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

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.

• Jezik: Angleški jezik
• Ključne besede: InhA inhibition, in silico docking, in vitro antimycobacterial activity, 2-isonicotinoylhydrazinecarboxamide, 5-(pyridine-4-yl)-1, 3, 4-oxadiazol-2-amine, tuberculosis
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FKKT - Fakulteta za kemijo in kemijsko tehnologijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2014
• Št. strani: Str. 3851-3868
• Številčenje: Vol. 19, iss. 4
• PID: 20.500.12556/RUL-129216
• UDK: 547.86.057:615.2
• ISSN pri članku: 1420-3049
• DOI: 10.3390/molecules19043851
• COBISS.SI-ID: 1698863
• Datum objave v RUL: 30.08.2021

Gradivo je del revije

• Naslov: Molecules
• Skrajšan naslov: Molecules
• Založnik: MDPI
• ISSN: 1420-3049
• COBISS.SI-ID: 18462981

Licence

• Licenca: CC BY 3.0, Creative Commons Priznanje avtorstva 3.0 Nedoločena
• Povezava: https://creativecommons.org/licenses/by/3.0/deed.sl
• Opis: Dovoljuje kopiranje in razširjanje vsebin v kakršnemkoli mediju in obliki. Dovoljuje remixanje, urejanje, predelava in vključevanje vsebine v lastna dela v vse namene, tudi komercialne. Primerno morate navesti avtorja, povezavo do licence in označiti spremembe, če so kakšne nastale. To lahko storite na kakršenkoli razumen način, vendar ne na način, ki bi namigoval na to, da dajalec licence podpira vas ali vašo uporabo dela. Ne smete uporabiti pravnih določil ali tehničnih ukrepov, ki bi pravno omejili ali onemogočilo druge, da bi storili karkoli, kar licenca dovoli.
• Začetek licenciranja: 01.04.2014

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: medicina, organska kemija, farmakologija, tuberkuloza, zdravila za zdravljenje tuberkuloze, protibakterijska aktivnost, heterociklične spojine, derivati karboksamida, derivati hidrazina, INH