Novel cyano- and N-isopropylamidino-substituted derivatives of benzo[b]thiophene-2-carboxanilides and benzo[b]thieno[2,3-c]quinolones: synthesis, photochemical synthesis, crystal structure determination, and antitumor evaluation. 2.
Derivatives of 3-chlorobenzo[b]thiophene-2-carboxanilides and their "cyclic" analogues benzo[b]thieno[2,3-c]quinolones were synthesized. Spectroscopic study of the interactions of some representatives of "cyclic" derivatives and their "acyclic" precursors with ds-DNA/RNA supported strong intercalative binding of the former and weak nonintercalative binding of the latter group of compounds. All tested compounds showed a certain antiproliferative effect on a series of human tumor cells and on a normal cell line. Among the compounds, those with one amidino-substituent have shown the best effect. The most active benzo[b]thieno[2,3-c]quinolones induced apparent S and G2/M arrests of the cell cycle, which resulted in apoptosis. These results strongly suggest that the compounds may act as topoisimerase "poisons", which is in good agreement with their intercalative mode of binding to ds-DNA/RNA, in contrast to the studied "acyclic"group of derivatives. 6a and 6d showed the best selectivity by inhibiting the growth of tumor cells but not of normal fibroblasts.
Jarak
Ivana
I
Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, P.O. Box 177, HR-10000 Zagreb, Croatia.
Kralj
Marijeta
M
Suman
Lidija
L
Pavlović
Gordana
G
Dogan
Jasna
J
Piantanida
Ivo
I
Zinić
Mladen
M
Pavelić
Kresimir
K
Karminski-Zamola
Grace
G
D000578:Amidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000813:Anilides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012313:RNA / Q000737:chemistry; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000578:Amidines; D000813:Anilides; D000970:Antineoplastic Agents; D009570:Nitriles; D015363:Quinolones; D013876:Thiophenes; D012313:RNA; D004247:DNA