Molecular Mechanism of Action of 2-Ferrocenyl-1,1-diphenylbut-1-ene on HL-60 Leukemia Cells
| Autor: | Danilo D. Rocha, Marília O. F. Goulart, Fabricia da Rocha Ferreira, Fabiane C. de Abreu, Letícia V. Costa-Lotufo, Felipe A. R. Rodrigues, Elizabeth A. Hillard, Alane Cabral Menezes de Oliveira, Emanuella Gomes da Silva, Gérard Jaouen, Pascal Pigeon |
|---|---|
| Přispěvatelé: | Universidade Federal de Alagoas = Federal University of Alagoas (UFAL), Universidade Federal do Ceará = Federal University of Ceará (UFC), Centre de Recherche Paul Pascal (CRPP), Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Charles Friedel, Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Parisien de Chimie Moléculaire (IPCM), Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2014 |
| Předmět: |
Metallocenes
Stereochemistry Antineoplastic Agents Apoptosis HL-60 Cells [CHIM.THER]Chemical Sciences/Medicinal Chemistry DNA Fragmentation 010402 general chemistry Cell morphology 01 natural sciences Biochemistry antitumor agents Drug Discovery medicine Humans [CHIM.COOR]Chemical Sciences/Coordination chemistry Ferrous Compounds General Pharmacology Toxicology and Pharmaceutics Cell Proliferation Pharmacology Leukemia ferrocenes 010405 organic chemistry Cell growth Chemistry bioelectrochemistry Organic Chemistry Hyperchromicity DNA Cell cycle G1 Phase Cell Cycle Checkpoints 0104 chemical sciences 3. Good health Mechanism of action Cell culture [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Biophysics Molecular Medicine DNA fragmentation medicine.symptom |
| Zdroj: | ChemMedChem ChemMedChem, Wiley-VCH Verlag, 2014, 9 (11), pp.2580-2586. ⟨10.1002/cmdc.201402219⟩ |
| ISSN: | 1860-7179 1860-7187 |
| Popis: | International audience; The aim of this work was to investigate the mechanism of action of 2-ferrocenyl-1,1-diphenylbut-1-ene (1) on HL-60 human leukemia cells. While inactive against noncancerous cells, 1 provoked a concentration-dependent decrease in viable tumor cells, primarily via apoptosis, as evidenced by analysis of cell morphology, activation of caspases3 and 7, increased DNA fragmentation, and externalization of phosphatidylserine. Necrosis was observed only at the highest tested concentration (4M). Compound 1 interfered with the cell cycle, causing an accumulation of cells in the G(1)/G(0) phase. Interaction of 1 with dsDNA and ssDNA was observed by differential pulse voltammetry and confirmed by hyperchromicity in the UV/Vis spectra of dsDNA, with an interaction constant of 2x10(4)M(-1). Both the organic analogue 1,1,2-triphenylbut-1-ene (2) and ferrocene were inactive against cancer and noncancer cell lines and did not react with DNA. These results reinforce the idea that the hybrid strategy of conjugating ferrocene to the structure of tamoxifen derivatives is advantageous in finding new substances with antineoplastic activity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text