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 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.
Rodríguez-Ciria
Marinela
M
Departamento de Quimica Organica I, Facultad de Quimica, Universidad Complutense, 28040 Madrid, Spain.
Sanz
Ana M
AM
Yunta
Maria J R
MJ
Gomez-Contreras
Fernando
F
Navarro
Pilar
P
Fernandez
Isabel
I
Pardo
Mercedes
M
Cano
Carmen
C
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000737:chemistry; D015195:Drug Design; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D008958:Models, Molecular; D010793:Phthalazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011073:Polyamines / Q000737:chemistry
D000970:Antineoplastic Agents; D007364:Intercalating Agents; D010793:Phthalazines; D011073:Polyamines; D004247:DNA