RESUMO
Synthesis and anticancer studies of three symmetrically and non-symmetrically substituted silver(I)-N-Heterocyclic carbene complexes of type [(NHC)2-Ag]PF6 (7-9) and their respective (ligands) benzimidazolium salts (4-6) are described herein. Compound 5 and Ag-NHC-complex 7 were characterized by the single crystal X-ray diffraction technique. Structural studies for 7 showed that the silver(I) center has linear C-Ag-C coordination geometry (180.00(10)o). Other azolium and Ag-NHC analogues were confirmed by H1 and C13-NMR spectroscopy. The synthesized analogues were biologically characterized for in vitro anticancer activity against three cancer cell lines including human colorectal cancer (HCT 116), breast cancer (MCF-7), and erythromyeloblastoid leukemia (K-562) cell lines and in terms of in vivo acute oral toxicity (IAOT) in view of agility and body weight of female rats. In vitro anticancer activity showed the values of IC50 in range 0.31-17.9 µM in case of K-562 and HCT-116 cancer cell lines and 15.1-35.2 µM in case of MCF-7 while taking commercially known anticancer agents 5-fluorouracil, tamoxifen, and betulinic acid which have IC50 values 5.2, 5.5, and 17.0 µM, respectively. In vivo study revealed vigor and agility of all test animals which explores the biocompatibility and non-toxicity of the test analogues.
Assuntos
Antineoplásicos/farmacologia , Metano/análogos & derivados , Prata/farmacologia , Animais , Antineoplásicos/química , Benzimidazóis/química , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células HCT116 , Humanos , Concentração Inibidora 50 , Células K562 , Ligantes , Células MCF-7 , Espectroscopia de Ressonância Magnética , Masculino , Metano/química , Metano/farmacologia , Estrutura Molecular , Ratos , Prata/química , Espectroscopia de Infravermelho com Transformada de Fourier , Relação Estrutura-Atividade , Difração de Raios XRESUMO
A cellular membrane affinity chromatography (CMAC) column has been created using cellular membrane fragments from a 1321N1 cell line stably transfected with the P2Y(1) receptor. The CMAC(1321N1(P2Y1)) column contained functional P2Y(1) and histamine 1 receptors, which independently bound receptor-specific ligands. The data obtained with the CMAC(1321N1(P2Y1)) column demonstrate that multiple-G-protein coupled receptor (GPCR) columns can be developed and used to probe interactions with the immobilized receptors and that endogenously expressed GPCRs can be used to create CMAC columns. The results also establish that the histamine 1 receptor can be immobilized with retention of ligand-specific binding.
