Next-generation heterocyclic electrophiles as small-molecule covalent MurA inhibitors

Péter Ábrányi-Balogh (Avtor), Aaron Keeley (Avtor), György G. Ferenczy (Avtor), László Petri (Avtor), Tímea Imre (Avtor), Katarina Grabrijan (Avtor), Martina Hrast (Avtor), Damijan Knez (Avtor), Janez Ilaš (Avtor), Stanislav Gobec (Avtor), György Keserü M. (Avtor)

Povzetek

Heterocyclic electrophiles as small covalent fragments showed promising inhibitory activity on the antibacterial target MurA (UDP-N-acetylglucosamine 1-carboxyvinyltransferase, EC:2.5.1.7). Here, we report the second generation of heterocyclic electrophiles: the quaternized analogue of the heterocyclic covalent fragment library with improved reactivity and MurA inhibitory potency. Quantum chemical reaction barrier calculations, GSH (L-glutathione) reactivity assay, and thrombin counter screen were also used to demonstrate and explain the improved reactivity and selectivity of the N-methylated heterocycles and to compare the two generations of heterocyclic electrophiles.

Ključne besede

kovalentni inhibitor;heterociklični elektrofili;označevanje cisteina;kvaternizacija;MurA;covalent inhibitor;heterocyclic electrophiles;cysteine labelling;quaternization;

Podatki

Jezik:	Angleški jezik
Leto izida:	2022
Tipologija:	1.01 - Izvirni znanstveni članek
Organizacija:	UL FFA - Fakulteta za farmacijo
UDK:	615.4:54:615.28
COBISS:	132462339
ISSN:	1424-8247
Št. ogledov:	8
Št. prenosov:	0
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarni jezik:	Slovenski jezik
Sekundarne ključne besede:	Farmacevtska kemija;Bakterijska rezistenca;
Vrsta dela (COBISS):	Članek v reviji
Strani:	10 str.
Letnik:	ǂVol. ǂ15
Zvezek:	ǂiss. ǂ12, art. 1484
Čas izdaje:	2022
DOI:	10.3390/ph15121484
ID:	17332121