Synthesis, photochemical synthesis, DNA binding and antitumor evaluation of novel cyano- and amidino-substituted derivatives of naphtho-furans, naphtho-thiophenes, thieno-benzofurans, benzo-dithiophenes and their acyclic precursors.
As a part of the research on the improvement of an alternative to conventional photodynamic therapy by light-induced formation of intercalators, we synthesized a series of novel heterocyclic compounds and their acyclic precursors. We now report details about their synthesis/characterization in respect to their potential of photoinduced cyclization, interactions with DNA and inhibition of the tumor cell growth in vitro. Among studied compounds only amidino-furyl-substituted phenyl acrylates were efficiently converted to the corresponding naphthofuranes, while their thiophene analogues, all non-charged derivatives and amidino-phenyl-substituted analogues didn't show acceptable photoconversion. The significantly stronger antiproliferative activity of cyclic analogues could be correlated to the property of these molecules to intercalate into DNA. The acyclic molecules did not show any interaction with DNA, correlating with the inferior biological activity, except for one cyano-bearing molecule.
Starcević
Kristina
K
Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, P.O. Box 177, HR-10000 Zagreb, Croatia. kstarcev@fkit.hr
Kralj
Marijeta
M
Piantanida
Ivo
I
Suman
Lidija
L
Pavelić
Kresimir
K
Karminski-Zamola
Grace
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010777:Photochemistry; D013055:Spectrophotometry, Infrared; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D005663:Furans; D013876:Thiophenes; D004247:DNA