Synthesis, antitumor evaluation and DNA binding studies of novel amidino-benzimidazolyl substituted derivatives of furyl-phenyl- and thienyl-phenyl-acrylates, naphthofurans and naphthothiophenes.
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.
Hranjec
Marijana
M
Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, P.O. Box 177, HR-10000 Zagreb, Croatia.
Starcević
Kristina
K
Piantanida
Ivo
I
Kralj
Marijeta
M
Marjanović
Marko
M
Hasani
Merima
M
Westman
Gunnar
G
Karminski-Zamola
Grace
G
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*
D000179:Acrylates; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D005663:Furans; D013876:Thiophenes; D004247:DNA