title: Interaction between bioactive compound 11a-N-tosyl-5-deoxi-pterocarpan (LQB-223) and Calf thymus DNA: Spectroscopic approach, electrophoresis and theoretical studies.
abstract: The interaction of small molecules with DNA has been quite important, since this biomolecule is currently the major target for a wide range of drugs in clinical use or advanced clinical research phase. Thus, the present work aimed to assess the interaction process between the bioactive compound 11a-N-tosyl-5-carba-pterocarpan, (LQB-223), that presents antitumor activity, with DNA, employing spectroscopic techniques, electrophoresis, viscosity and theoretical studies. Through UV-vis and molecular fluorescence spectroscopy, it was possible to infer that the preferential quenching mechanism was static, characterized by non-fluorescent supramolecular complex formation between the LQB-223 and DNA. The binding constant was 1.94∙103Lmol-1(30°C) and, according to the thermodynamic parameters, the main forces involved in the interaction process are hydrophobic. Potassium iodide assay, competition with ethidium bromide, fluorescence contact energy transfer and melting temperature profile of DNA were employed to evaluate the binding mode. Except for KI assay, all results obtained indicated minor groove as the preferential binding mode of LQB-223 to DNA. These observations were supported by ionic strength assay, viscosity and molecular dynamics and docking studies. Finally, electrophoresis analysis demonstrated that the interaction does not promote DNA fragmentation, but it leads to variation in the migration profile after increasing the ligand concentration.
authors.affiliation: Chemistry and Biotechnology Institute (IQB), Federal University of Alagoas (UFAL), Campus A.C. Simões, Tabuleiro dos Martins, 57072-970, Maceió-AL, Brazil.
authors.forename: Marina M
authors.initials: MM
authors.lastname: Silva
authors.affiliation: Chemistry and Biotechnology Institute (IQB), Federal University of Alagoas (UFAL), Campus A.C. Simões, Tabuleiro dos Martins, 57072-970, Maceió-AL, Brazil.
authors.forename: Eduarda O O
authors.initials: EOO
authors.lastname: Nascimento
authors.affiliation: Chemistry and Biotechnology Institute (IQB), Federal University of Alagoas (UFAL), Campus A.C. Simões, Tabuleiro dos Martins, 57072-970, Maceió-AL, Brazil.
authors.forename: Edeíldo F
authors.initials: EF
authors.lastname: Silva
authors.affiliation: Chemistry and Biotechnology Institute (IQB), Federal University of Alagoas (UFAL), Campus A.C. Simões, Tabuleiro dos Martins, 57072-970, Maceió-AL, Brazil; Nursing and Pharmacy School (ESENFAR), Federal University of Alagoas (UFAL), Campus A.C. Simões, Tabuleiro dos Martins, 57072-970, Maceió-AL, Brazil.
authors.forename: João Xavier de
authors.initials: JX
authors.lastname: Araújo
authors.affiliation: Nursing and Pharmacy School (ESENFAR), Federal University of Alagoas (UFAL), Campus A.C. Simões, Tabuleiro dos Martins, 57072-970, Maceió-AL, Brazil.
authors.forename: Camilla C
authors.initials: CC
authors.lastname: Santana
authors.affiliation: Nursing and Pharmacy School (ESENFAR), Federal University of Alagoas (UFAL), Campus A.C. Simões, Tabuleiro dos Martins, 57072-970, Maceió-AL, Brazil.
authors.forename: Luciano Aparecido M
authors.initials: LAM
authors.lastname: Grillo
authors.affiliation: Department of Chemistry, Pontifical Catholic University of Rio de Janeiro, Rua Marquês de São Vicente, 225, Gávea, 22435-900, Rio de Janeiro, RJ, Brazil.
authors.forename: Rafaela S
authors.initials: RS
authors.lastname: de Oliveira
authors.affiliation: Bio-organic Chemistry Laboratory, Research Institute of Natural Products Health Sciences Center, Block H, Federal University of Rio de Janeiro, 21941-590, Rio de Janeiro, RJ, Brazil.
authors.forename: Paulo
authors.initials: P
authors.lastname: R R Costa
authors.affiliation: Department of Chemistry, Pontifical Catholic University of Rio de Janeiro, Rua Marquês de São Vicente, 225, Gávea, 22435-900, Rio de Janeiro, RJ, Brazil.
authors.forename: Camilla D
authors.initials: CD
authors.lastname: Buarque
authors.affiliation: Chemistry and Biotechnology Institute (IQB), Federal University of Alagoas (UFAL), Campus A.C. Simões, Tabuleiro dos Martins, 57072-970, Maceió-AL, Brazil. Electronic address: josue@iqb.ufal.br.
authors.forename: Josué Carinhanha C
authors.initials: JCC
authors.lastname: Santos
authors.affiliation: Chemistry and Biotechnology Institute (IQB), Federal University of Alagoas (UFAL), Campus A.C. Simões, Tabuleiro dos Martins, 57072-970, Maceió-AL, Brazil. Electronic address: figueiredo.isis@gmail.com.
authors.forename: Isis M
authors.initials: IM
authors.lastname: Figueiredo
mesh_terms: D000818:Animals; D001483:Base Sequence; D002417:Cattle; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004586:Electrophoresis; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009994:Osmolar Concentration; D036343:Pterocarpans / Q000378:metabolism* / Q000494:pharmacology; D013057:Spectrum Analysis; D014783:Viscosity
chemical_list: C000593733:11a-N-tosyl-5-deoxi-pterocarpan; D036343:Pterocarpans; D004247:DNA; C427203:calf thymus DNA
keywords: 11a-N-arylsulfonyl-tetrahydro-5H-benzo[a]carbazole; 11a-N-tosyl-5-carbapterocarpan; CT DNA interaction; Electrophoresis; Spectroscopic techniques; Theoretical studies