BIOMAT Database Logo BIOMAT Database Logo

Design and synthesis of a novel series of pyranonaphthoquinones as topoisomerase II catalytic inhibitors. 2008

Sandra Jiménez-Alonso, and Haydee Chávez Orellana, and Ana Estévez-Braun, and Angel G Ravelo, and Elisa Pérez-Sacau, and Felix Machín
Instituto Universitario de Bio-Orgánica "Antonio González", Universidad de La Laguna, Avda. Astrofísico Fco, Sánchez 2, 38206 La Laguna, Tenerife, Spain.

On the basis of previous pharmacophore modeling studies of naphthoquinones derivatives, we have designed and synthesized a new set of pyranonaphthoquinones. These compounds were obtained through a direct and highly efficient approach based on an intramolecular domino Knoevenagel hetero Diels-Alder reaction from lawsone (2-hydroxynaphthoquinone) and a variety of aldehydes containing an alkene. The synthesized pyranonaphthoquinones were evaluated against the alpha isoform of human topoisomerase II (hTopoIIalpha). Among the 11 derivatives studied, we found that six of them act as catalytic inhibitors of the enzyme in vitro. These six derivatives strongly preclude the enzyme from decatenating or relaxing suitable substrates. Finally, we correlate their active/inactive status with docking studies of these novel compounds into the ATPase domain of hTopoIIalpha.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D009285 Naphthoquinones Naphthalene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. Naphthalenediones,Naphthazarins,Naphthoquinone
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011714 Pyrans Pyran
D002384 Catalysis The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction. Catalyses
D004250 DNA Topoisomerases, Type II DNA TOPOISOMERASES that catalyze ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. These enzymes bring about relaxation of the supercoiled DNA and resolution of a knotted circular DNA duplex. DNA Topoisomerase (ATP-Hydrolysing),DNA Topoisomerase II,DNA Topoisomerase II alpha,DNA Topoisomerase II beta,DNA Type 2 Topoisomerase,TOP2A Protein,TOP2B Protein,Topoisomerase II,Topoisomerase II alpha,Topoisomerase II beta,Type II DNA Topoisomerase,alpha, Topoisomerase II,beta, Topoisomerase II
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D004278 DNA, Superhelical Circular duplex DNA isolated from viruses, bacteria and mitochondria in supercoiled or supertwisted form. This superhelical DNA is endowed with free energy. During transcription, the magnitude of RNA initiation is proportional to the DNA superhelicity. DNA, Supercoiled,DNA, Supertwisted,Supercoiled DNA,Superhelical DNA,Supertwisted DNA
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

Related Publications

Sandra Jiménez-Alonso, and Haydee Chávez Orellana, and Ana Estévez-Braun, and Angel G Ravelo, and Elisa Pérez-Sacau, and Felix Machín
Design, synthesis, and biological evaluation of 1,3-diarylisoquinolines as novel topoisomerase I catalytic inhibitors.
January 2018, European journal of medicinal chemistry,
Sandra Jiménez-Alonso, and Haydee Chávez Orellana, and Ana Estévez-Braun, and Angel G Ravelo, and Elisa Pérez-Sacau, and Felix Machín
Design, Synthesis and Anti-Tumor Activity of Novel Benzimidazole-Chalcone Hybrids as Non-Intercalative Topoisomerase II Catalytic Inhibitors.
July 2020, Molecules (Basel, Switzerland),
Sandra Jiménez-Alonso, and Haydee Chávez Orellana, and Ana Estévez-Braun, and Angel G Ravelo, and Elisa Pérez-Sacau, and Felix Machín
Design, synthesis and biological evaluation of novel perimidine o-quinone derivatives as non-intercalative topoisomerase II catalytic inhibitors.
October 2019, Bioorganic chemistry,
Sandra Jiménez-Alonso, and Haydee Chávez Orellana, and Ana Estévez-Braun, and Angel G Ravelo, and Elisa Pérez-Sacau, and Felix Machín
Design, synthesis and biological evaluation of novel glycosylated diphyllin derivatives as topoisomerase II inhibitors.
January 2012, European journal of medicinal chemistry,
Sandra Jiménez-Alonso, and Haydee Chávez Orellana, and Ana Estévez-Braun, and Angel G Ravelo, and Elisa Pérez-Sacau, and Felix Machín
Novel coumarin-pyrazole carboxamide derivatives as potential topoisomerase II inhibitors: Design, synthesis and antibacterial activity.
September 2018, European journal of medicinal chemistry,
Sandra Jiménez-Alonso, and Haydee Chávez Orellana, and Ana Estévez-Braun, and Angel G Ravelo, and Elisa Pérez-Sacau, and Felix Machín
A new phenolic series of indenopyridinone as topoisomerase inhibitors: Design, synthesis, and structure-activity relationships.
October 2018, Bioorganic & medicinal chemistry,
Sandra Jiménez-Alonso, and Haydee Chávez Orellana, and Ana Estévez-Braun, and Angel G Ravelo, and Elisa Pérez-Sacau, and Felix Machín
Design, Synthesis, and Anticancer Evaluation of Novel Indole Derivatives of Ursolic Acid as Potential Topoisomerase II Inhibitors.
April 2020, International journal of molecular sciences,
Sandra Jiménez-Alonso, and Haydee Chávez Orellana, and Ana Estévez-Braun, and Angel G Ravelo, and Elisa Pérez-Sacau, and Felix Machín
Design and synthesis of Aza-boeravinone derivatives as potential novel topoisomerase I inhibitors.
May 2022, Bioorganic chemistry,
Sandra Jiménez-Alonso, and Haydee Chávez Orellana, and Ana Estévez-Braun, and Angel G Ravelo, and Elisa Pérez-Sacau, and Felix Machín
Catalytic inhibitors of DNA topoisomerase II.
October 1998, Biochimica et biophysica acta,
Sandra Jiménez-Alonso, and Haydee Chávez Orellana, and Ana Estévez-Braun, and Angel G Ravelo, and Elisa Pérez-Sacau, and Felix Machín
A series of enediynes as novel inhibitors of topoisomerase I.
July 2001, Bioorganic & medicinal chemistry,
Copied contents to your clipboard!