Thieno[3,2-b]pyridines are present in bioactive molecules including in antitumor compounds. Herein, by C-C Pd-catalyzed Suzuki-Miyaura cross-coupling of methyl 3-bromothieno[3,2-b]pyridine-2-carboxylate with (Het)Ar pinacolboranes, trifluoro potassium boronate salts or boronic acids, novel methyl 3-(hetero)arylthieno[3,2-b]pyridine-2-carboxylates 1a-1f (Ar= Ph, p-Me-, p-OMe-, p-CF_3-, p-Cl- or p-CN-C₆H₄, respectively), 1g and 1h (HetAr= pyridin-4-yl and furan-3-yl, respectively) were synthesized in good to high yields and fully characterized.

The antitumor potential of all compounds was evaluated in human tumor cell lines from pancreatic (PANC1 and BxPC3), non-small cell lung (NCI-H460) and triple negative breast (MDA-MB-231 and MDA-MB-468) cancers.

Results showed that 1e (Ar =p-Cl-C₆H₄) inhibited MDA-MB-231 cells growth (GI₅₀=13 µM), while 1f (Ar=p-CN-C₆H₄) and 1h (HetAr=furan-3yl) inhibited MDA-MB-468 cells growth (GI₅₀ = 8 and 5 µM, respectively), using the Sulforhodamine B assay. Those compounds, at their GI₅₀ concentrations, did not cause toxicity against non-tumorigenic MCF12-A cells, thus further studies were conducted at their GI₅₀. Compound 1e did not alter the cell cycle profile of MDA-MB-231 cells (determined by flow cytometry following PI staining) but increased γ-H2A.X expression (determined by Western blot), which is suggestive of DNA damage. Moreover, 1e reduced the size of xenografts of MDA-MD-231 tumor cells using the in ovo CAM (Chick Chorioallantoic Membrane) assay. Compound 1h increased the G2/M phase with concomitant decrease in the G0/G1 phase of MDA-MB-468 cells cycle (and increased p21 expression when tested at 2xGI₅₀ concentration). Compound 1f did not alter the cell cycle-profile nor induced apoptosis of MDA-MB-468.cells. Our data suggest that the potential antitumor activity of these compounds should be further studied.