Novel Cyano- andN-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

Abstract

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.

Palladium(II) Catalyzed Cyclization-Carbonylation-Cyclization Coupling Reaction of (ortho-Alkynyl Phenyl) (Methoxymethyl) Sulfides Using Molecular Oxygen as the Terminal Oxidant

“…We are currently investigating further biological studies of the synthesized compounds 2. Benzo [b]thiophene skeletons are an important class of S-heterocycles [15][16][17][18] and are found in a variety of drugs, pesticides, and biologically active compounds that exhibit various interesting biological properties [19][20][21][22][23][24]. Diaryl ketone scaffolds are also important motifs in natural products and pharmaceuticals [25][26][27][28][29][30] (Figure 1).…”

Novel pentamidine derivatives: Synthesis, anti-tumor properties and polynucleotide-binding activities

“…Unlike their benzothiophene and thienothiophene anilide analogues, the cyano-and amidinomonosubstituted compounds 3, 5 and 6 exhibited no antiproliferative activity producing only modest growth inhibition against HeLa or MCF-7 lines, predominantly at the highest tested concentration, pointing towards the importance of benzothiophene and thienothiophene moieties for the antiproliferative activity of that class of compounds [17,18]. On the other hand, prolongation of the amido-scaffold (9, 10) resulted in markedly stronger antiproliferative effect towards certain cell lines, especially MCF-7.…”

“…Modified procedure was used for the synthesis of the cyano-substituted amides 11 and 17. Cyanosubstituted carboxamide 3 was converted to the corresponding amidines under the Pinner conditions [17]. Treatment of 3 with dry HCl gas in anhydrous EtOH gave the imidate ester, which was than treated with dry ammonia gas to produce amidino-substituted 2-furancarboxamide 5, or with excess of iso-propylamine to give iso-propylamidino substituted carboxamide 6.…”

“…Recently, working in the field of benzothieno and thienothienoquinolones, new intercalators with antiproliferative activity, we described the synthesis of a number of their precursors, cyano and amidino substituted 3-chlorobenzo [b]thiophene- [17], thieno [2,3-b]and thieno [3,2-b]thiophene-2-carboxanilides [18] which were found to exhibit interesting antiproliferative properties themselves. They were found to bind to polynucleotides in a weak nonintercalative way, and the mechanism of their antiproliferative activity is currently under investigation.…”

Synthesis, Antiviral and Antitumor Activity of 2‐Substituted‐5‐amidino‐benzimidazoles.

“…The solvent (DMSO) was also tested for eventual inhibitory activity by adjusting its concentration to be the same as in working concentrations. After 72 hours of incubation the cell growth rate was evaluated by performing the MTT assay, which detects dehydrogenase activity in viable cells, as described previously 35,36 . The absorbance (OD, optical density) was measured on a microplate reader at 570 nm.…”