Dialkylaminoalkylindolonaphthyridines as potential antitumour agents: synthesis, cytotoxicity and DNA binding properties.
The synthesis of new planar derivatives characterised by the presence of an indolonaphthyridine nucleus, carrying a dimethylaminoethyl or a dimethylaminopropyl side chain is reported. The antiproliferative activity of the new products was tested by means of an in vitro assay on human tumour cell lines (HL-60 and HeLa). A number of compounds (1a-d, 1h) showed IC(50) values comparable to that obtained with the well-known drug ellipticine on the HL-60 cell line. The interaction with DNA was also investigated. Linear flow dichroism measurements allowed us to understand the interaction geometry. The thermodynamic parameters of the binding process, i.e. intrinsic binding constant and exclusion parameter, were determined by fluorimetric titration.
Dipartimento di Scienze Farmaceutiche, Università di Padova, Via Marzolo 5, 35131 Padua, Italy. lisa.dallavia@unipd.it
Lisa
L
Dalla Via
Ornella
O
Gia
Sebastiano
S
Marciani Magno
Antonio
A
Da Settimo
Giampaolo
G
Primofiore
Federico
F
Da Settimo
Francesca
F
Simorini
Anna Maria
AM
Marini
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003500:Cyclization; D004273:DNA, Neoplasm / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D005470:Fluorometry; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D010084:Oxidation-Reduction; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D009287:Naphthyridines; D016159:Tumor Suppressor Protein p53