Synthesis and evaluation of tumor cell growth inhibition of methyl 3-amino-6-[(hetero)arylethynyl]thieno[3,2-b]pyridine-2-carboxylates. Structure-activity relationships, effects on the cell cycle and apoptosis.
The methyl 3-amino-6-bromothieno[3,2-b]pyridine-2-carboxylate, recently reported by some of us, was reacted in Sonogashira couplings with several (hetero)arylacetylenes. The growth inhibitory activity of the novel methyl 3-amino-6-[(hetero)arylethynyl]thieno[3,2-b]pyridine-2-carboxylates obtained was evaluated on three human tumor cell lines (MCF-7, NCI-H460, A375-C5). The para-methoxyphenyl and the ortho- and para-aminophenyl derivatives were the most promising compounds, and their effects were further studied regarding alterations in the normal cell cycle distribution and induction of apoptosis in the NCI-H460 cell line. All three compounds altered cell cycle distribution and the ortho-aminophenyl derivative was further shown to induce apoptosis in the same cell line.
Centro de Química, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal. mjrpq@quimica.uminho.pt
Maria-João R P
MJ
Queiroz
Ricardo C
RC
Calhelha
Luís A
LA
Vale-Silva
Eugénia
E
Pinto
Gabriela M
GM
Almeida
M Helena
MH
Vasconcelos
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002264:Carboxylic Acids