Synthesis, in vitro antiproliferative activity and DNA-interaction of benzimidazoquinazoline derivatives as potential anti-tumor agents.
The synthesis of benzimidazoquinazoline derivatives bearing different alkylamino side chains is reported. All new compounds tested by means of an in vitro assay exhibit antiproliferative activity toward human tumor cell lines. The cytotoxic effect depends on the type of side chain inserted in the planar nucleus and in some cases it is comparable to that of the well-known drug ellipticine. In order to understand the mechanism of action of these compounds, the interaction with DNA has been investigated. Linear flow dichroism measurements allowed us to verify the formation of a molecular complex with DNA and the corresponding geometry of interaction. Intrinsic binding constants have also been evaluated by performing fluorimetric titrations.
Dalla Via
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Department of Pharmaceutical Sciences, University of Padua, Via Marzolo 5, 35131 Padua, Italy.
Gia
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O
Magno
S M
SM
Da Settimo
A
A
Marini
A M
AM
Primofiore
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G
Da Settimo
F
F
Salerno
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S
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry; D004273:DNA, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D004273:DNA, Neoplasm; D011799:Quinazolines; D004247:DNA