title: Synthesis, Anti-Breast Cancer Activity, and Molecular Docking Study of a New Group of Acetylenic Quinolinesulfonamide Derivatives.
abstract: 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)-2H-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-[N-methyl-N-(3-propynyl)sulfamoyl]quinoline shows significant antiprolierative activity against T47D cells with IC50values of 0.07 µM. In addition, 2-(3-Propynylthio)-6-[N-methyl-N-(3-propynyl)sulfa-moyl]quinoline and 2-(3-propynylseleno)-6-[N-methyl-N-(3-propynyl)sulfamoyl]quinoline display highly effective atitumor activity against MDA-MB-231 cells, with IC50values 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.
authors.affiliation: Department of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland. kmarciniec@sum.edu.pl.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Marciniec
authors.affiliation: Department of Physical Pharmacy, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland. bpawelczak@sum.edu.pl.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Pawełczak
authors.affiliation: Department of Cell Biology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jedności 8, 41-200 Sosnowiec, Poland. mlatocha@sum.edu.pl.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Latocha
authors.affiliation: Department of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland. skrzypek@sum.edu.pl.
authors.forename: Leszek
authors.initials: L
authors.lastname: Skrzypek
authors.affiliation: Department of Physical Pharmacy, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland. mmaciazek@sum.edu.pl.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Maciążek-Jurczyk
authors.affiliation: Department of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland. boryczka@sum.edu.pl.
authors.forename: Stanisław
authors.initials: S
authors.lastname: Boryczka
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000737:chemistry / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1 / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011804:Quinolines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000480:Alkynes; D000970:Antineoplastic Agents; D011804:Quinolines; D013449:Sulfonamides; C037219:quinoline; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1
keywords: alkynes; anticancer; cytochrome P450; quinolinesulfonamides; virtual screening