Synthesis of Novel Methyl 3-(hetero)arylthieno[3,2-b]pyridine-2-carboxylates and Antitumor Activity Evaluation: Studies In Vitro and In Ovo Grafts of Chick Chorioallantoic Membrane (CAM) with a Triple Negative Breast Cancer Cell Line

• Autor(a) principal: Silva, Bruna R.
• Data de Publicação: 2021
• Outros Autores: Rebelo, Rita, Rodrigues, Juliana M., Xavier, Cristina P. R., Vasconcelos, M. Helena, Queiroz, Maria João R. P.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: https://hdl.handle.net/1822/72679
• topic: anticancer activity; Suzuki-Miyaura coupling; thieno[3; 2-b]pyridines; triple negative breast cancer; Thieno[3,2-b]pyridines; Science & Technology

A series of novel functionalized methyl 3-(hetero)arylthieno[3,2-<i>b</i>]pyridine-2-carboxylates <b>2a</b>–<b>2h</b> were synthesized by C-C Pd-catalyzed Suzuki-Miyaura cross-coupling of methyl 3-bromothieno[3,2-<i>b</i>]pyridine-2-carboxylate with (hetero)aryl pinacol boranes, trifluoro potassium boronate salts or boronic acids. Their antitumoral potential was evaluated in two triple negative breast cancer (TNBC) cell lines—MDA-MB-231 and MDA-MB-468, by sulforhodamine B assay. Their effects on the non-tumorigenic MCF-12A cells were also evaluated. The results demonstrated that three compounds caused growth inhibition in both TNBC cell lines, with little or no effect against the non-tumorigenic cells. The most promising compound was further studied concerning possible effects on cell viability (by trypan blue exclusion assay), cell proliferation (by bromodeoxyuridine assay) and cell cycle profile (by flow cytometry). The results demonstrated that the GI₅₀ concentration of compound <b>2e</b> (13 μM) caused a decreased in MDA-MB-231 cell number, which was correlated with a decreased in the % of proliferating cells. Moreover, this compound increased G0/G1 phase and decreased S phases, when compared to control cells (although was not statistic significant). Interestingly, compound <b>2e</b> also reduced tumor size using an in ovo CAM (chick chorioallantoic membrane) model. This work highlights the potential antitumor effect of a novel methyl 3-arylthieno[3,2-<i>b</i>]pyridine-2-carboxylate derivative.