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

• Published in: Molecules (Basel, Switzerland) Switzerland), 2021-03, Vol.26 (6), p.1594
• Main Authors: Silva, Bruna R, Rebelo, Rita, Rodrigues, Juliana M, Xavier, Cristina P R, Vasconcelos, M Helena, Queiroz, Maria-João R P
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; anticancer activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor activity; Assaying; Breast cancer; Bromodeoxyuridine; Cancer therapies; Carboxylates; Cell cycle; Cell Cycle - drug effects; Cell growth; Cell Line; Cell Line, Tumor; Cell number; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell viability; Chorioallantoic membrane; Chorioallantoic Membrane - surgery; Cross coupling; Cytotoxicity; Drug Screening Assays, Antitumor; Epidermal growth factor; Estrogens; Female; Flow cytometry; G1 phase; Humans; Kinases; Mammary Glands, Human - drug effects; Mammary Glands, Human - pathology; Membranes; Molecular Structure; Neoplasm Transplantation; Potassium; Pyridines; Salts; Structure-Activity Relationship; Sulforhodamine; Suzuki-Miyaura coupling; thieno[3,2-b]pyridines; Thienopyridines - chemical synthesis; Thienopyridines - chemistry; Thienopyridines - pharmacology; triple negative breast cancer; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - pathology; Tumor cell lines
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26061594

A series of novel functionalized methyl 3-(hetero)arylthieno[3,2- ]pyridine-2-carboxylates - were synthesized by C-C Pd-catalyzed Suzuki-Miyaura cross-coupling of methyl 3-bromothieno[3,2- ]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 GI concentration of compound (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 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- ]pyridine-2-carboxylate derivative.