Square planar compounds containing 3,3-biisoquinoline: synthesis and G-quadruplexes DNA binding studies

• Grant number: 13/26203-5
• Support type: Scholarships abroad - Research
• Effective date (Start): August 01, 2014
• Effective date (End): March 31, 2015
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Adelino Vieira de Godoy Netto
• Grantee: Adelino Vieira de Godoy Netto
• Host: Michael John Hannon
• Home Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Local de pesquisa : University of Birmingham, England

Abstract

This work deals with the synthesis, characterization and human telomeric G-quadruplex DNA binding studies on new chelates of general formulae [M(bisq)(N-X)]+n (M = Pd(II), Pt(II); bisq = 3,32-biisoquinoline; N-X (X = C) = C2,N-benzylidenemethylamine, C2,N-benzaldehydeoxime type-ligands; N-X (X = S) = thiosemicarbazide type ligands; n = 1,2). These complexes exhibit pre-conceived structural requirements suitable for acting as telomeric G-quadruplex DNA binders and, eventually, as new anti-telomerase agents. The characterization of the functionalized ligands and their metal-based derivatives will be carried out by elemental analysis, IR and NMR spectroscopies, ESI/MS spectrometry, and single crystals X-ray diffraction crystallography. Selectivity for G-quadruplexes (G4-DNA) over duplex DNA structures (dsDNA) will be evaluated by determining the intrinsic DNA binding constants (Kb) via UV-Vis spectroscopy. Circular dicroism will be obtained in order to evidence topology adopted by G4 and to verify if the complex contributes to the formation and stabilization of G-4 structure. The affinity of the complexes for G4-DNA over dsDNA will be evaluated by the required concentration to displace 50% of thiazole orange (G4DC50 and dsDC50, respectively) using the Fluorescent Intercalator Displacement assay (FID) and the selectivity will be estimate by the dsDC50/G4DC50 ratio. Electrophoresis mobility shift assays will be employed to determine conformational changes in DNA, including the formation or destabilization of a quadruplex, and the binding between ligands and quadruplexes. The citotoxicity of compounds towards tumor cell sensitive (ex. A2780) and resistant to cisplatin (ex. A2780cisR) will be determined by M.T.T. assay. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SILVA, DEBORA E. S.; BECCENERI, AMANDA B.; SANTIAGO, JOAO V. B.; GOMES NETO, JOSE A.; ELLENA, JAVIER; COMINETTI, MARCIA R.; PEREIRA, JOSE C. M.; HANNON, MICHAEL J.; NETTO, ADELINO V. G. Silver(I) complexes of 3-methoxy-4-hydroxybenzaldehyde thiosemicarbazones and triphenylphosphine: structural, cytotoxicity, and apoptotic studies. DALTON TRANSACTIONS, v. 49, n. 45, p. 16474-16487, DEC 7 2020. Web of Science Citations: 1.