Evaluation of the DNA Alkylation Properties of a Chlorambucil-Conjugated Cyclic Pyrrole-Imidazole Polyamide.
DNA alkylator
DNA recognition
alkylation
antitumor agents
drug delivery
Journal
Chemistry (Weinheim an der Bergstrasse, Germany)
ISSN: 1521-3765
Titre abrégé: Chemistry
Pays: Germany
ID NLM: 9513783
Informations de publication
Date de publication:
05 Feb 2021
05 Feb 2021
Historique:
received:
01
10
2020
revised:
30
10
2020
pubmed:
5
11
2020
medline:
2
3
2021
entrez:
4
11
2020
Statut:
ppublish
Résumé
Hairpin pyrrole-imidazole polyamides (hPIPs) and their chlorambucil (Chb) conjugates (hPIP-Chbs) can alkylate DNA in a sequence-specific manner, and have been studied as anticancer drugs. Here, we conjugated Chb to a cyclic PIP (cPIP), which is known to have a higher binding affinity than the corresponding hPIP, and investigated the DNA alkylation properties of the resulting cPIP-Chb using the optimized capillary electrophoresis method and conventional HPLC product analysis. cPIP-Chb conjugate 3 showed higher alkylation activity at its binding sites than did hPIP-Chb conjugates 1 and 2. Subsequent HPLC analysis revealed that the alkylation site of conjugate 3, which was identified by capillary electrophoresis, was reliable and that conjugate 3 alkylates the N3 position of adenine as do hPIP-Chbs. Moreover, conjugate 3 showed higher cytotoxicity against LNCaP prostate cancer cells than did conjugate 1 and cytotoxicity comparable to that of conjugate 2. These results suggest that cPIP-Chbs could be novel DNA alkylating anticancer drugs.
Identifiants
pubmed: 33145851
doi: 10.1002/chem.202004421
doi:
Substances chimiques
Imidazoles
0
Nylons
0
Pyrroles
0
Chlorambucil
18D0SL7309
DNA
9007-49-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2782-2788Subventions
Organisme : Japan Society for the Promotion of Science
ID : 16H06356
Organisme : Japan Agency for Medical Research and Development
ID : 18am0301005
Informations de copyright
© 2020 Wiley-VCH GmbH.
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