ALL libraries (COBIB.SI union bibliographic/catalogue database)
-
Nature-inspired substituted 3-(imidazol-2-yl) morpholines targeting human topoisomerase IIα [Elektronski vir] : dynophore-derived discoveryHerlah, Barbara, farmacevtka ...The molecular nanomachine, human DNA topoisomerase IIα, plays a crucial role in replication, transcription, and recombination by catalyzing topological changes in the DNA, rendering it an optimal ... target for cancer chemotherapy. Current clinical topoisomerase II poisons often cause secondary tumors as side effects due to the accumulation of double-strand breaks in the DNA, spurring the development of catalytic inhibitors. Here, we used a dynamic pharmacophore approach to develop catalytic inhibitors targeting the ATP binding site of human DNA topoisomerase IIα. Our screening of a library of nature-inspired compounds led to the discovery of a class of 3-(imidazol-2-yl) morpholines as potent catalytic inhibitors that bind to the ATPase domain. Further experimental and computational studies identified hit compound 17, which exhibited selectivity against the human DNA topoisomerase IIα versus human protein kinases, cytotoxicity against several human cancer cells, and did not induce DNA double-strand breaks, making it distinct from clinical topoisomerase II poisons. This study integrates an innovative natural product-inspired chemistry and successful implementation of a molecular design strategy that incorporates a dynamic component of ligand-target molecular recognition, with comprehensive experimental characterization leading to hit compounds with potential impact on the development of more efficient chemotherapies.Source: Biomedicine & pharmacotherapy [Elektronski vir]. - ISSN 1950-6007 (Vol. 175, [article no.] 116676, Jun. 2024, str. 1-18)Type of material - e-article ; adult, seriousPublish date - 2024Language - englishCOBISS.SI-ID - 196316419
Author | Herlah, Barbara, farmacevtka ... |
Title | Nature-inspired substituted 3-(imidazol-2-yl) morpholines targeting human topoisomerase IIα [Elektronski vir] : dynophore-derived discovery |
Publication date | 2024-06-01 |
COBISS.SI-ID | 196316419 |
Publication version in repository | Publisher's version |
Publication licence | Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International |
Embargo | Immediate publication for public |
Project(s) from which the publication was funded
Title | Acronym | Project ID | Funder |
---|---|---|---|
Dinamični model molekulskega stroja DNA topoizomeraze tipa II in razvoj katalitičnih inhibitorjev | J1-4402-2022 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Vrednotenje prehodnih stanj proteinov | J1-4400-2022 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Molekulske simulacije, bioinformatika in načrtovanje zdravilnih učinkovin | P1-0012-2019 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Folding in dinamika biomolekularnih sistemov | P1-0010-2019 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Ekotoksiologija, toksikološka genomika in karcinogeneza | P1-0245-2019 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
Files that belong to the publication
Costs of publication
Cost type | Total cost | Payments |
---|---|---|
APC – Article Processing Charge | 3060.00 € |
3060.00 € : Kemijski inštitut |
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|---|
Herlah, Barbara, farmacevtka | 54668 |
Janežič, Matej, kemik, 1990- | |
Ogris, Iza | 50459 |
Golič Grdadolnik, Simona | 08329 |
Kološa, Katja | 29297 |
Žabkar, Sonja | 55689 |
Žegura, Bojana | 20767 |
Perdih, Andrej, farmacevt | 25493 |
Source: Personal bibliographies
and: SICRIS
Select pickup location:
Material pickup by post
Delivery address:
Address is missing from the member's data.
The address retrieval service is currently unavailable, please try again.
By clicking the "OK" button, you will confirm the pickup location selected above and complete the reservation process.
By clicking the "OK" button, you will confirm the above pickup location and delivery address, and complete the reservation process.
By clicking the "OK" button, you will confirm the address selected above and complete the reservation process.
Notification
Automatic login and reservation service currently not available. You can reserve the material on the Biblos portal or try again here later.
Select pickup location
The material from the parent unit is free. If the material is delivered to the pickup location from another unit, the library may charge you for this service.
Pickup location | Material status | Reservation |
---|
Reservation in progress
Please wait a moment.
Reservation was successful.
Reservation failed.
Reservation...
Membership card:
Pickup location: