title: New arylated benzo[h]quinolines induce anti-cancer activity by oxidative stress-mediated DNA damage.
abstract: The anti-cancer activity of the benzo[h]quinolines was evaluated on cultured human skin cancer (G361), lung cancer (H460), breast cancer (MCF7) and colon cancer (HCT116) cell lines. The inhibitory effect of these compounds on the cell growth was determined by the MTT assay. The compounds 3e, 3f, 3h and 3j showed potential cytotoxicity against these human cancer cell lines. Effect of active compounds on DNA oxidation and expression of apoptosis related gene was studied. We also developed a quantitative method to measure the activity of cyclin-dependent kinases-2 (CDK2) by western blotting in the presence of active compound. In addition, molecular docking revealed that benzo[h]quinolines can correctly dock into the hydrophobic pocket of the targets receptor protein aromatase and CDK2, while their bioavailability/drug-likeness was predicted to be acceptable but requires future optimization. These findings reveal that benzo[h]quinolines act as anti-cancer agents by inducing oxidative stress-mediated DNA damage.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur-342005, India.|Department of Pharmacy, College of Pharmacy, Gachon University, 155 Gaetbeol-ro, Incheon, Korea.
authors.forename: Dharmendra K
authors.initials: DK
authors.lastname: Yadav
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi-110029, India.
authors.forename: Reeta
authors.initials: R
authors.lastname: Rai
authors.affiliation: Plasma Bioscience Research Center, Kwangwoon University, Nowon-Gu, Seoul 139-701, Korea.
authors.forename: Naresh
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Department of Chemistry, University of Delhi-110007 India.
authors.forename: Surjeet
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur-342005, India.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Misra
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur-342005, India.
authors.forename: Praveen
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Plasma Bioscience Research Center, Kwangwoon University, Nowon-Gu, Seoul 139-701, Korea.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Shaw
authors.affiliation: Computer Science Department, Catholic University of Murcia (UCAM) E30107, Murcia, Spain.
authors.forename: Horacio
authors.initials: H
authors.lastname: Pérez-Sánchez
authors.affiliation: School of Biomedical Sciences, Curtin Health Innovation Research Institute and Curtin Institute for Computation, Curtin University: GPO Box U1987, Perth WA 6845, Australia.
authors.forename: Ricardo L
authors.initials: RL
authors.lastname: Mancera
authors.affiliation: Plasma Bioscience Research Center, Kwangwoon University, Nowon-Gu, Seoul 139-701, Korea.
authors.forename: Eun Ha
authors.initials: EH
authors.lastname: Choi
authors.affiliation: Department of Pharmacy, College of Pharmacy, Gachon University, 155 Gaetbeol-ro, Incheon, Korea.
authors.forename: Mi-Hyun
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Chemistry, University of Delhi-110007 India.
authors.forename: Ramendra
authors.initials: R
authors.lastname: Pratap
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D045325:HCT116 Cells; D006801:Humans; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects*; D011804:Quinolines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011804:Quinolines; D018844:Cyclin-Dependent Kinases