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

Povzetek

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.

Ključne besede

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;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL FKKT - Fakulteta za kemijo in kemijsko tehnologijo
UDK: 547.86.057:615.2
COBISS: 1698863 Povezava se bo odprla v novem oknu
ISSN: 1420-3049
Št. ogledov: 231
Št. prenosov: 67
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: medicina;organska kemija;farmakologija;tuberkuloza;zdravila za zdravljenje tuberkuloze;protibakterijska aktivnost;heterociklične spojine;derivati karboksamida;derivati hidrazina;INH;
Vrsta dela (COBISS): Članek v reviji
Strani: str. 3851-3868
Letnik: ǂVol. ǂ19
Zvezek: ǂno. ǂ4
Čas izdaje: 2014
DOI: 10.3390/molecules19043851
ID: 13296243