Novel bis-phenanthridine derivatives with easily tunable linkers, study of their interactions with DNA and screening of antiproliferative activity

Series of novel peptide-bridged bis-phenanthridine derivatives as well as corresponding monomers were prepared by solid phase peptide synthesis, which allowed easy and fast tuning of compound properties. Interactions of new derivatives with double stranded DNA were strongly structure-dependent, amon...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2010-06, Vol.45 (6), p.2671-2676
Main Authors: Dukši, Marko, Baretić, Domagoj, Čaplar, Vesna, Piantanida, Ivo
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents - chemistry
Antineoplastic Agents - metabolism
Antineoplastic Agents - pharmacology
Biological and medical sciences
Cattle
Cell Line, Tumor
Cell Proliferation - drug effects
DNA - chemistry
DNA - metabolism
DNA binding
Drug Screening Assays, Antitumor
Fluorescence
General aspects
Humans
Medical sciences
Nucleic Acid Denaturation
Pharmacology. Drug treatments
Phenanthridine
Phenanthridines - chemistry
Phenanthridines - metabolism
Phenanthridines - pharmacology
Solid phase synthesis
Transition Temperature
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Summary:Series of novel peptide-bridged bis-phenanthridine derivatives as well as corresponding monomers were prepared by solid phase peptide synthesis, which allowed easy and fast tuning of compound properties. Interactions of new derivatives with double stranded DNA were strongly structure-dependent, among which the most interesting is bis-phenanthridine derivative forming intramolecular excimer, with specific fluorescence band sensitive to the pH as well as on the interactions with ds-DNA. Moreover, at variance to commonly high cytotoxic effects of phenanthridine derivatives, here studied monomeric as well as bis-phenanthridine derivatives exhibited negligible antiproliferative activity on a panel of human cell lines, which makes them promising lead compounds for development of new spectrophotometric markers. [Display omitted]
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2010.02.017