RRC ID 57980
著者 Othman DIA, Selim KB, El-Sayed MA, Tantawy AS, Amen Y, Shimizu K, Okauchi T, Kitamura M.
タイトル Design, Synthesis and Anticancer Evaluation of New Substituted Thiophene-Quinoline Derivatives.
ジャーナル Bioorg Med Chem
Abstract A series of new isoxazolyl, triazolyl and phenyl based 3-thiophen-2-yl-quinoline derivatives were synthesized adopting click chemistry approach. In addition, the synthesis of new useful synthon, (2-chloroquinolin-3-yl) (thiophen-2-yl) methanol, is reported. The obtained compounds were characterized by spectral data analysis and evaluated for their anticancer activity. All the derivatives were subjected to in vitro MTT cytotoxicity screening assay against a panel of four different human cancer cell lines, liver (HepG-2), colon (HCT-116), human cervical cancer (HeLa) and breast (MCF-7). Out of a library of 17 compounds, two compounds have been identified as potent and selective cytotoxic agents against HeLa and MCF-7 cell lines. SAR studies for such hybridized analogues were investigated and phenyl derivatives were proved to be more potent than isoxazole and triazole derivatives. Furthermore, the promising compounds were selected for in vitro inhibition of EGFR-TK and Topo II enzymes. Also, they were subjected to cell cycle arrest analysis and apoptosis assay on MCF-7 cells. Our recent finding highlights these thiophene-quinoline analogues as a promising class of compounds for further studies concerning new anticancer therapies.
巻・号 27(19)
ページ 115026
公開日 2019-10-1
DOI 10.1016/j.bmc.2019.07.042
PII S0968-0896(19)31149-6
PMID 31416740
MeSH Antineoplastic Agents / chemical synthesis Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology* Apoptosis / drug effects Caspase 3 / metabolism Caspase 7 / metabolism Caspase 9 / metabolism Cell Proliferation / drug effects DNA Topoisomerases, Type II / metabolism Drug Design Drug Screening Assays, Antitumor Enzyme Inhibitors / chemical synthesis Enzyme Inhibitors / chemistry Enzyme Inhibitors / pharmacology ErbB Receptors / metabolism G2 Phase Cell Cycle Checkpoints / drug effects Humans MCF-7 Cells Molecular Structure Quinolines / chemical synthesis Quinolines / chemistry Quinolines / pharmacology* Structure-Activity Relationship Thiophenes / chemical synthesis Thiophenes / chemistry Thiophenes / pharmacology*
IF 3.073
引用数 2
リソース情報
ヒト・動物細胞 MCF7(RCB1904) HeLa Hep G2 HCT116(RCB2979)