thienopyridine and Breast-Neoplasms

Glycosphingolipid expression differs between human breast cancer stem cells (CSC) and cancer non-stem cells (non-CSC). We performed studies of viability, type of cell death, cancer stem cell percent and glycosphingolipid expression on CSC and non-CSC after treatment of MDA-MB-231 and MDA-MB-453 triple-negative breast cancer cells with a newly developed thienopyridine anticancer compound (3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide, 1). Compound 1 was cytotoxic for both breast cancer cell lines and the majority of cells died by treatment-induced apoptosis. The percent of cancer stem cells and number of formed mammospheres was significantly lower. Glycosphingolipids IV

Topics: Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Female; Glycosphingolipids; Humans; Metabolic Networks and Pathways; Molecular Structure; Neoplastic Stem Cells; Pyridines; Tumor Cells, Cultured

Iron oxide nanoparticles, with diameters around 12nm, were synthesized by coprecipitation method. The magnetic properties indicate a superparamagnetic behavior with a coercive field of 9.7Oe and a blocking temperature of 118K. Both aqueous and solid magnetoliposomes containing magnetite nanoparticles have sizes below 150nm, suitable for biomedical applications. Interaction between both types of magnetoliposomes and models of biological membranes was proven. A new antitumor compound, a diarylurea derivative of thienopyridine, active against breast cancer, was incorporated in both aqueous and solid magnetoliposomes, being mainly located in the lipid membrane. A promising application of these magnetoliposomes in oncology is anticipated, allowing a combined therapeutic approach, using both chemotherapy and magnetic hyperthermia.

Topics: Breast Neoplasms; Ferric Compounds; Humans; Hyperthermia, Induced; Liposomes; Magnetite Nanoparticles; Pyridines; Temperature

As a part of ongoing studies in developing new anticancer agents, novel 1,2-dihydropyridine 4, thienopyridine 5, isoquinolines 6-20, acrylamide 21, thiazolidine 22, thiazoles 23-29 and thiophenes 33-35 bearing a biologically active quinoline nucleus were synthesized. The structure of newly synthesized compounds was confirmed on the basis of elemental analyses and spectral data. All the newly synthesized compounds were evaluated for their cytotoxic activity against the breast cancer cell line MCF7. 2,3-Dihydrothiazole-5-carboxamides 27, 25, 4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (34), 1,2-dihydroisoquinoline-7-carbonitrile (7), 5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide (35), 1,2-dihydroisoquinoline-7-carbonitrile (6), 2-cyano-3-(dimethylamino)-N-(quinolin-3-yl)acrylamide (21), 1,2-dihydroisoquinoline-7-carbonitriles (11) and (8) exhibited higher activity (IC50 values of 27-45 μmol L-1) compared to doxorubicin (IC50 47.9 μmol L-1). LQ quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (12), 2-thioxo-2,3-dihydrothiazole-5-carboxamide (28) and quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (15) show activity comparable to doxorubicin, while (quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (9), 2,3-dihydrothiazole-5-carboxamide (24), thieno [3,4-c] pyridine-4(5H)-one (5), cyclopenta[b]thiophene-3-carboxamide (33) and (quinolin-3-yl)-6-stryl-1,2-dihydroisoquinoline-7-carbonitrile (10) exhibited moderate activity, lower than doxorubicin.

Topics: Antineoplastic Agents; Breast Neoplasms; Cell Survival; Dose-Response Relationship, Drug; Drug Design; Female; Humans; Inhibitory Concentration 50; Isoquinolines; MCF-7 Cells; Models, Molecular; Molecular Structure; Pyridines; Quinolines; Structure-Activity Relationship; Thiazoles; Thiazolidines; Thiophenes