title: Molecular docking studies of the interaction between propargylic enol ethers and human DNA topoisomerase IIα.
abstract: Having identified a novel human DNA topoisomerase IIα (TOP2) catalytic inhibitor from a small and structure-focused library of propargylic enol ethers, we decided to analyze if the chirality of these compounds plays a determinant role in their antiproliferative activity. In this study, we describe for the first time the synthesis of the corresponding enantiomers and the biological evaluation against a panel of representative human solid tumor cell lines. Experimental results show that chirality does not influence the reported antiproliferative activity of these compounds. Docking studies of corresponding enantiomers against TOP2 reinforce the finding that the biological effect is not chiral-dependent and that these family of compounds seem to act as TOP2 catalytic inhibitors.
authors: Instituto Universitario de Bio-Orgánica Antonio González (IUBO-AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, La Laguna, Spain.
authors: Gastón
authors: G
authors: Silveira-Dorta
authors: Inês J
authors: IJ
authors: Sousa
authors: Carla
authors: C
authors: Ríos-Luci
authors: Víctor S
authors: VS
authors: Martín
authors: Miguel X
authors: MX
authors: Fernandes
authors: José M
authors: JM
authors: Padrón
mesh_terms: D000475:Alkenes / Q000737:chemistry / Q000494:pharmacology; D000480:Alkynes / Q000737:chemistry* / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000737:chemistry*; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004250:DNA Topoisomerases, Type II / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D004987:Ethers / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D052250:Nitric Oxide Synthase Type III; D000075223:Poly-ADP-Ribose Binding Proteins; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D000480:Alkynes; D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D004987:Ethers; D000075223:Poly-ADP-Ribose Binding Proteins; C531209:propargyl ether; D052250:Nitric Oxide Synthase Type III; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human
keywords: Antitumor agents; Chirality; Docking studies; Enzyme inhibitors; Topoisomerase IIα