Synthesis and cytotoxic activity of N,N-bis-(3-[N-(4-chlorobenzo[g]-phthalazin-1-yl)]aminopropyl)-N-methylamine: a new potential DNA bisintercalator

The synthesis of a new series of mono- and dinuclear 1-alkylamino-4-chlorobenzo[g]phthalazine derivatives 7-10 containing flexible polyaminic chains is reported. It has been achieved by the reaction of 1,4-dichlorobenzo[g]phthalazine with the corresponding polyamines. In vitro antitumoral activity a...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2003-05, Vol.11 (10), p.2143-2148
Main Authors: Rodríguez-Ciria, Marinela, Sanz, Ana M, Yunta, Maria J R, Gomez-Contreras, Fernando, Navarro, Pilar, Fernandez, Isabel, Pardo, Mercedes, Cano, Carmen
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - pharmacology
Cell Death - drug effects
Cell Division - drug effects
DNA - chemistry
Drug Design
HT29 Cells - drug effects
Humans
Intercalating Agents - chemical synthesis
Intercalating Agents - pharmacology
Models, Molecular
Phthalazines - chemical synthesis
Phthalazines - pharmacology
Polyamines - chemistry
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Summary:The synthesis of a new series of mono- and dinuclear 1-alkylamino-4-chlorobenzo[g]phthalazine derivatives 7-10 containing flexible polyaminic chains is reported. It has been achieved by the reaction of 1,4-dichlorobenzo[g]phthalazine with the corresponding polyamines. In vitro antitumoral activity against HT-29 human colon carcinoma cells was evaluated and showed best results for compound 10, in which two heteroaromatic units are linked by a N-methylsubstituted polyaminic chain. Molecular modelling of the complexes of 9 and 10 with DNA strongly suggests the possibility of bisintercalation, and also that the N-methyl group of 10 plays an important role in the formation of a specially stable DNA complex.
ISSN:0968-0896