Synthesis, Anti-Breast Cancer Activity, and Molecular Docking Study of a New Group of Acetylenic Quinolinesulfonamide Derivatives

• Published in: Molecules (Basel, Switzerland) Switzerland), 2017-02, Vol.22 (2), p.300-300
• Main Authors: Marciniec, Krzysztof, Pawełczak, Bartosz, Latocha, Małgorzata, Skrzypek, Leszek, Maciążek-Jurczyk, Małgorzata, Boryczka, Stanisław
• Format: Article
• Language: English
• Subjects: alkynes; Alkynes - chemistry; anticancer; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiproliferatives; Benzene; Binding Sites; Breast cancer; Catalytic Domain; Cell Line, Tumor; Cell Proliferation - drug effects; Cisplatin; Cytochrome P-450 CYP1A1 - chemistry; Cytochrome P-450 CYP1A1 - metabolism; Cytochrome P-450 CYP1B1 - chemistry; Cytochrome P-450 CYP1B1 - metabolism; Cytochrome P450; Cytochromes P450; Cytotoxicity; Dose-Response Relationship, Drug; Humans; Hydrogen Bonding; Isoenzymes; Molecular Conformation; Molecular docking; Molecular Docking Simulation; Protein Binding; Quinoline; Quinolines - chemistry; quinolinesulfonamides; Structure-Activity Relationship; Sulfonamides - chemical synthesis; Sulfonamides - chemistry; Sulfonamides - pharmacology; Tumor cell lines; virtual screening
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules22020300

In this study, a series of regioisomeric acetylenic sulfamoylquinolines are designed, synthesized, and tested in vitro for their antiproliferative activity against three human breast cacer cell lines (T47D, MCF-7, and MDA-MB-231) and a human normal fibroblast (HFF-1) by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2 -5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay. The antiproliferative activity of the tested acetylenic quinolinesulfonamides is comparable to that of cisplatin. The bioassay results demonstrate that most of the tested compounds show potent antitumor activities, and that some compounds exhibit better effects than the positive control cisplatin against various cancer cell lines. Among these compounds, 4-(3-propynylthio)-7-[ -methyl- -(3-propynyl)sulfamoyl]quinoline shows significant antiprolierative activity against T47D cells with IC values of 0.07 µM. In addition, 2-(3-Propynylthio)-6-[ -methyl- -(3-propynyl)sulfa-moyl]quinoline and 2-(3-propynylseleno)-6-[ -methyl- -(3-propynyl)sulfamoyl]quinoline display highly effective atitumor activity against MDA-MB-231 cells, with IC values of 0.09 and 0.50 µM, respectively. Furthermore, most of the tested compounds show a weak cytotoxic effect against the normal HFF-1 cell line. Additionally, in order to suggest a mechanism of action for their activity, all compounds are docked into the binding site of two human cytochrome P450 (CYP) isoenzymes. These data indicate that some of the title compounds display significant cytotoxic activity, possibly targeting the CYPs pathways.