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

Abstract

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

Synthesis, Characterization and Apoptosis Capabilities of a Novel Naphthoquinone‐Derived Compound in Triple‐Negative Breast Cancer

“…The new 2-(4-(benzo[d] [1,3]dioxol-5-ylmethyl)piperazin-1yl)-3-bromonaphthalen-1,4-dione (ZP-2) was synthesized in red color with 65 % yield. In the FT-IR spectrum of compound ZP-2, two strong quinonic carbonyl absorptions were observed at 1632 and 1670 cm À 1 .…”

“…The most aggressive and invasive subtype, it is highly resistant to drugs and has a poor prognosis. [3] Although knowledge regarding TNBC has advanced with molecular classification, specific treatment options remain inadequate. [4] Research is necessary into the synthesis of novel drugs possessing greater selectivity and efficacy with fewer adverse effects, as well as the development of therapeutic approaches for the treatment of metastatic TNBC.…”

Pirfenidone Sensitizes NCI-H460 Non-Small Cell Lung Cancer Cells to Paclitaxel and to a Combination of Paclitaxel with Carboplatin

“…Cell proliferation was assessed using the 5-bromo-2′-deoxyuridine (BrdU) incorporation assay, according to the described protocol [ 37 , 44 , 45 ]. For that, NCI-H460 cells were plated in 6-well plates at a previously determined optimal cell concentration (5 × 10 4 cells/mL) and incubated for 24 h. Then, cells were subjected to the desired treatments for 48 h. Nearly 4 h before cell collection, cells of each condition were incubated with BrdU (Merck Life Science, Darmstadt, Germany; B5002) at a final concentration of 10 μM.…”

“…Cell cycle profile was assessed by flow cytometry following propidium iodide (PI) staining, according to the described protocol [ 37 , 38 , 44 , 45 ]. For that, NCI-H460 cells were plated in 6-well plates at a previously determined optimal cell concentration (5 × 10 4 cells/mL) and incubated for 24 h. Then, cells were treated with the desired conditions for 48 h. After the incubation period, cells of each condition were collected, centrifuged (1200 rpm for 5 min at 4 °C) and fixed with ice-cold 70% ethanol (Fischer Scientific, Hampton, NH, USA; E/0650DF/C17) at 4 °C for a period of at least 12 h. Then, cells were centrifuged at the previously described conditions and each cell pellet was resuspended in a PBS solution containing 0.1 mg/mL RNase A (Invitrogen, Waltham, MA, USA; 12091021) and 5 µg/mL PI (Merck Life Science, Darmstadt, Germany; 537060) and kept in the dark for at least 30 min.…”

Exploring the Potential of Montmorillonite as an Antiproliferative Nanoagent against MDA-MB-231 and MCF-7 Human Breast Cancer Cells

“…Despite advances in diagnosis and treatment, breast cancer is still the leading cause of cancer-related death in women [1,2], highlighting the importance of developing new therapeutic strategies for this disease.…”