Molecular Docking and Biological Evaluation of Functionalized benzo[h]quinolines as Colon Cancer Agents

As a part of our drug discovery program, we have synthesized various 2-amino-benzo[h]quinoline-6-carbonitrile derivatives and analyzed them on human colon cancer cells in the form of percentage inhibition at different concentration gradient and time of incubation. Anticancer activity of these derivatives against the human HCT116 cancer cells using in vitro employing standard MTT assay. Compounds 3a-3e showed significant anti-cancer activity especially compound 3b and3d exhibit the good inhibitory activity on HCT116 cells. Additionally, docking study was performed on colon cancer target cyclin-dependent kinase-2 to understand the cytotoxic mechanism of action of active compounds.

[1]  Dong Woon Kim,et al.  Design, synthesis and inhibitory activities of naringenin derivatives on human colon cancer cells. , 2013, Bioorganic & medicinal chemistry letters.

[2]  G Roma,et al.  1,8-Naphthyridines IV. 9-substituted N,N-dialkyl-5-(alkylamino or cycloalkylamino) [1,2,4]triazolo[4,3-a][1, 8]naphthyridine-6-carboxamides, new compounds with anti-aggressive and potent anti-inflammatory activities. , 2000, European journal of medicinal chemistry.

[3]  Richard B. Halberg,et al.  Phospholipid Ether Analogs for the Detection of Colorectal Tumors , 2014, PloS one.

[4]  Sung Ho Ryu,et al.  G2 arrest and apoptosis by 2-amino-N-quinoline-8-yl-benzenesulfonamide (QBS), a novel cytotoxic compound. , 2005, Biochemical pharmacology.

[5]  Eun Ha Choi,et al.  Enhancement of glucose uptake in skeletal muscle L6 cells and insulin secretion in pancreatic hamster-insulinoma-transfected cells by application of non-thermal plasma jet , 2013 .

[6]  C. Tzeng,et al.  Synthesis and antibacterial evaluation of certain quinolone derivatives. , 2001, Journal of medicinal chemistry.

[7]  S. Alqasoumi,et al.  Novel quinolines and pyrimido[4,5-b]quinolines bearing biologically active sulfonamide moiety as a new class of antitumor agents. , 2010, European journal of medicinal chemistry.

[8]  Michael Reth,et al.  Hydrogen peroxide as second messenger in lymphocyte activation , 2002, Nature Immunology.

[9]  Jacques Yves Gauthier,et al.  Practical Route to a New Class of LTD4 Receptor Antagonists , 1996 .

[10]  S. Alqasoumi,et al.  Synthesis and biological evaluation of 2-amino-7,7-dimethyl 4-substituted-5-oxo-1-(3,4,5-trimethoxy)-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile derivatives as potential cytotoxic agents. , 2009, Bioorganic & medicinal chemistry letters.

[11]  Yang Liu,et al.  Cost-Effectiveness of Colorectal Cancer Screening Protocols in Urban Chinese Populations , 2014, PloS one.

[12]  Feroz Khan,et al.  QSAR and docking based semi-synthesis and in vivo evaluation of artemisinin derivatives for antimalarial activity. , 2014, Current drug targets.

[13]  Feroz Khan,et al.  Design, synthesis and in vitro evaluation of 18β-glycyrrhetinic acid derivatives for anticancer activity against human breast cancer cell line MCF-7. , 2014, Current medicinal chemistry.

[14]  Brijesh Kumar,et al.  One-Pot Chemoselective Synthesis of Arylated Benzo[h]quinolines , 2014 .

[15]  Ruhima Khan,et al.  Highly Regioselective Diels–Alder Reaction of 9-Substituted Anthracenes with Citraconic Anhydride , 2014 .

[16]  Yu Cheng,et al.  Synthesis, cytotoxic activities and structure-activity relationships of topoisomerase I inhibitors: indolizinoquinoline-5,12-dione derivatives. , 2008, Bioorganic & medicinal chemistry.

[17]  Mohammad Ahmadian,et al.  Synthesis and evaluation of antitumor activity of novel N-acyllavendamycin analogues and quinoline-5,8-diones. , 2007, Bioorganic & medicinal chemistry.

[18]  J. Falgueyret,et al.  Quinolines as potent 5-lipoxygenase inhibitors: synthesis and biological profile of L-746,530. , 1998, Bioorganic & medicinal chemistry letters.