Object's details: Dimeric Benzodiazepines as Peptide Mimetics to Overcome p53-Dependent Drug Resistance of Tumors

Provider:Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

Description

Title:
Dimeric Benzodiazepines as Peptide Mimetics to Overcome p53-Dependent Drug Resistance of Tumors
Creator:
Speina, Elzbieta;
Wilczek, Marcin;
Mieczkowski, Adam
Description:
: Benzodiazepines that consist of one α- and one β-amino acid residues linked together in a seven-membered heterocyclic ring could be treated as small, rigid, cyclic dipeptides capable of exhibiting a wide range of biological activities. During our research on novel analogues of anthramycin, a tricyclic antibiotic benzodiazepine, we developed the synthesis of two benzodiazepine dimers, obtained through the cyclization of appropriate linear tripeptides. The synthesized compounds were tested on a panel of seven cancer and normal cell lines. The developed molecules exhibited promising cytotoxic activity against the lung cancer cell lines A549 and NCI-H1299 and the epidermoid carcinoma cell line A-431. Moreover, they showed significant selectivity compared to the reference cell lines (BJ—human normal skin fibroblasts and MRC-5—human normal lung cell line). When tested on two isogenic cell lines, HCT116 and HCT116p53−/− (colon cancer), contrary to cisplatin being used as a positive control, the obtained compounds showed a cytotoxic effect independent of the p53 protein status. For the above reasons, the obtained compounds can be considered a new group of promising anticancer agents, useful in the fight against p53-dependent drug resistance in cancers. They can also be treated as convenient, leading structures suitable for further optimization and searching for more active and selective molecules.
Object availability:
free access
Date:
2023.02.03
Type:
Article;
PeerReviewed
Language:
English;
eng
Format:
application/pdf
Publisher:
MDPI
Relation: http://eprints.ibb.waw.pl/2250 ;https://www.mdpi.com/journal/biomolecules ;
10.3390/biom13020291
Subject:
QD Chemistry;
RM Therapeutics. Pharmacology
Identifier: http://eprints.ibb.waw.pl/2250/1/40a.pdf ;
Speina, Elzbieta and Wilczek, Marcin and Mieczkowski, Adam (2023) Dimeric Benzodiazepines as Peptide Mimetics to Overcome p53-Dependent Drug Resistance of Tumors. Biomolecules, 13 (2). p. 291. ISSN 2218-273X
Data provider:
Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

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Object's details: Dimeric Benzodiazepines as Peptide Mimetics to Overcome p53-Dependent Drug Resistance of Tumors

Description

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