title: Synthesis, antitumor evaluation and DNA binding studies of novel amidino-benzimidazolyl substituted derivatives of furyl-phenyl- and thienyl-phenyl-acrylates, naphthofurans and naphthothiophenes.
abstract: A series of amidino-substituted benzimidazoles, related to furyl-phenyl- and thienyl-phenyl-acrylates, naphthofurans and naphthothiophenes were prepared, their antitumor evaluation and interactions with ct-DNA have been investigated. All tested compounds show differential and strong antitumor activity without apparent difference depending on their structures. Interestingly, the MCF-7 tumor cell line is highly sensitive to all compounds. Compounds 6-9 showed noticeable selectivity in regard to normal fibroblasts (WI 38). Compounds 4-9 interact with ct-DNA by more binding modes, whose mutual distribution is dependent on the compound/DNA ratio. The "acyclic"4-6 and "cyclic" compound 7 interact mostly within the minor groove of DNA, although partial intercalation of 6 and 7 cannot be excluded. The "cyclic" compounds 8 and 9 intercalate between DNA base pairs at high excess of DNA over compounds.
authors.affiliation: Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, P.O. Box 177, HR-10000 Zagreb, Croatia.
authors.forename: Marijana
authors.initials: M
authors.lastname: Hranjec
authors.forename: Kristina
authors.initials: K
authors.lastname: Starcević
authors.forename: Ivo
authors.initials: I
authors.lastname: Piantanida
authors.forename: Marijeta
authors.initials: M
authors.lastname: Kralj
authors.forename: Marko
authors.initials: M
authors.lastname: Marjanović
authors.forename: Merima
authors.initials: M
authors.lastname: Hasani
authors.forename: Gunnar
authors.initials: G
authors.lastname: Westman
authors.forename: Grace
authors.initials: G
authors.lastname: Karminski-Zamola
mesh_terms: D000179:Acrylates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013696:Temperature; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000179:Acrylates; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D005663:Furans; D013876:Thiophenes; D004247:DNA