Vaš brskalnik ne omogoča JavaScript!
JavaScript je nujen za pravilno delovanje teh spletnih strani. Omogočite JavaScript ali pa uporabite sodobnejši brskalnik.
Nacionalni portal odprte znanosti
Odprta znanost
DiKUL
slv
|
eng
Iskanje
Brskanje
Novo v RUL
Kaj je RUL
V številkah
Pomoč
Prijava
Exploring the chemical space of benzothiazole-based DNA gyrase B inhibitors
ID
Skok, Žiga
(
Avtor
),
ID
Barančokova, Michaela
(
Avtor
),
ID
Benek, Ondřej
(
Avtor
),
ID
Durante Cruz, Cristina
(
Avtor
),
ID
Tammela, Päivi
(
Avtor
),
ID
Tomašič, Tihomir
(
Avtor
),
ID
Zidar, Nace
(
Avtor
),
ID
Peterlin-Mašič, Lucija
(
Avtor
),
ID
Zega, Anamarija
(
Avtor
),
ID
Kikelj, Danijel
(
Avtor
),
ID
Ilaš, Janez
(
Avtor
)
PDF - Predstavitvena datoteka,
prenos
(2,22 MB)
MD5: 2F36CA91727B2E04DE1406F41A26D19F
URL - Izvorni URL, za dostop obiščite
https://pubs.acs.org/doi/pdf/10.1021/acsmedchemlett.0c00416
URL - Izvorni URL, za dostop obiščite
https://pubs.acs.org/doi/abs/10.1021/acsmedchemlett.0c00416#
Galerija slik
Izvleček
We designed and synthesized a series of inhibitors of the bacterial enzymes DNA gyrase and DNA topoisomerase IV, based on our recently published benzothiazole-based inhibitor bearing an oxalyl moiety. To improve the antibacterial activity and retain potent enzymatic activity, we systematically explored the chemical space. Several strategies of modification were followed: varying substituents on the pyrrole carboxamide moiety, alteration of the central scaffold, including variation of substitution position and, most importantly, modification of the oxalyl moiety. Compounds with acidic, basic, and neutral properties were synthesized. To understand the mechanism of action and binding mode, we have obtained a crystal structure of compound 16a, bearing a primary amino group, in complex with the N-terminal domain of E. coli gyrase B (24 kDa) (PDB: 6YD9). Compound 15a, with a low molecular weight of 383 Da, potent inhibitory activity on E. coli gyrase (IC50 = 9.5 nM), potent antibacterial activity on E. faecalis (MIC = 3.13 [micro]M), and efflux impaired E. coli strain (MIC = 0.78 [micro]M), is an important contribution for the development of novel gyrase and topoisomerase IV inhibitors in Gram-negative bacteria.
Jezik:
Angleški jezik
Ključne besede:
DNA gyrase
,
topoisomerase IV
,
GyrB
,
ParE
,
antibacterial benzothiazole
Vrsta gradiva:
Članek v reviji
Tipologija:
1.01 - Izvirni znanstveni članek
Organizacija:
FFA - Fakulteta za farmacijo
Status publikacije:
Objavljeno
Različica publikacije:
Objavljena publikacija
Leto izida:
2020
Št. strani:
Str. 2433-2440
Številčenje:
Vol. 11, iss. 12
PID:
20.500.12556/RUL-141912
UDK:
615.4:54
ISSN pri članku:
1948-5875
DOI:
10.1021/acsmedchemlett.0c00416
COBISS.SI-ID:
32932099
Datum objave v RUL:
11.10.2022
Število ogledov:
374
Število prenosov:
72
Metapodatki:
Citiraj gradivo
Navadno besedilo
BibTeX
EndNote XML
EndNote/Refer
RIS
ABNT
ACM Ref
AMA
APA
Chicago 17th Author-Date
Harvard
IEEE
ISO 690
MLA
Vancouver
:
Kopiraj citat
Objavi na:
Gradivo je del revije
Naslov:
ACS medicinal chemistry letters
Založnik:
American Chemical Society
ISSN:
1948-5875
COBISS.SI-ID:
2959217
Sekundarni jezik
Jezik:
Slovenski jezik
Ključne besede:
topoizomeraza IV
,
giraza DNA
,
antibakterijski benzotiazol
,
inibitorji giraze B
Projekti
Financer:
ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:
P1-0208-2015
Naslov:
Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin
Financer:
EC - European Commission
Program financ.:
European Commission
Številka projekta:
642620
Naslov:
Interdisciplinary Training Network for Validation of Gram-Negative Antibacterial Targets
Akronim:
INTEGRATE
Financer:
Drugi - Drug financer ali več financerjev
Program financ.:
Academy of Finland
Številka projekta:
277001
Naslov:
Phenotypic biosensor-based HTS and mode of action analysis by metabolomics and transcriptomics for enhancing antimicrobial drug discovery against Gram-negative bacteria
Financer:
Drugi - Drug financer ali več financerjev
Program financ.:
EU FP7 Integrated Project MAREX
Številka projekta:
FP7-KBBE-2009-3- 245137
Financer:
Drugi - Drug financer ali več financerjev
Program financ.:
Wellcome Trust
Številka projekta:
110072/Z/15/Z
Financer:
Drugi - Drug financer ali več financerjev
Program financ.:
Biotechnology and Biosciences Research Council (UK) Institute Strategic Programme Grant B
Številka projekta:
BB/P012523/1
Podobna dela
Podobna dela v RUL:
Podobna dela v drugih slovenskih zbirkah:
Nazaj