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Dimeric Benzodiazepines as Peptide Mimetics to Overcome p53-Dependent Drug Resistance of Tumors

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


Official URL: https://www.mdpi.com/journal/biomolecules


: 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.

Item Type:Article
Subjects:Q Science > QD Chemistry
R Medicine > RM Therapeutics. Pharmacology
Divisions:Department of Biophysics
ID Code:2250
Deposited By: Dr Adam Mieczkowski
Deposited On:20 Feb 2023 12:45
Last Modified:20 Feb 2023 12:45

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