RESUMO

Previously, ferrocene incorporation into the principal structural component of biologically active molecules resulted in enhanced cytotoxic activity against hormone-dependent MCF-7 and T-47D and hormone-independent MDA-MB-231 breast-cancer cell lines. Here we explore 4 new ferrocene estrogen conjugates at position 16 of the estrogen hormone and compared them to the previously reported ferrocene estrogen conjugate 3-ferrocenyl-estra-1,3,5(10)-triene-17ß-ol. The ferrocene conjugate 16-ferrocenylidene-3-hydroxyestra-1,3,5(10)-trien-17-one was synthesized using estrone and ferrocene carboxaldehyde as starting materials in 86% yield. This ferrocene complex was used as the starting material for the synthesis of new ferrocene estrogen conjugates by a short linker group at position 16 of the estrogen hormone. The position and stereochemistry of the linker was verified by its crystal structure. The ferrocene redox behavior, in vitro studies on breast-cancer cell lines and docking studies on ERα are presented. The data suggest that the ferrocene conjugates presented, either at position 3 or 16 of the estrogen, could serve as vectors and can be recognized by ERα as a delivery mechanism into the cell. These new ferrocene hormone conjugates showed cytotoxic activity comparable to that of conventional therapeutic drugs such as tamoxifen and cisplatin.

Assuntos

Antineoplásicos/síntese química , Neoplasias da Mama/tratamento farmacológico , Estrogênios/química , Compostos Ferrosos/síntese química , Metalocenos/síntese química , Aminoácidos/química , Antineoplásicos/metabolismo , Transporte Biológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Desenho de Fármacos , Receptor alfa de Estrogênio/efeitos dos fármacos , Estrogênios/metabolismo , Feminino , Compostos Ferrosos/metabolismo , Humanos , Metalocenos/metabolismo , Simulação de Acoplamento Molecular/métodos , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade

RESUMO

A new ferrocene complex, 16-ferrocenylmethyl-3ß-hy-droxy-estra-1,3,5(10)-trien-17-one dimethyl sulfoxide monosolvate, [Fe(C5H5)(C24H27O2)]·C2H6OS, has been synthesized and structurally characterized by single-crystal X-ray diffraction techniques. The mol-ecule crystallizes in the space group P21 with one mol-ecule of dimethyl sulfoxide. A hydrogen bond links the phenol group and the dimethyl sulfoxide O atom, with an O⋯O distance of 2.655 (5) Å. The ferrocene group is positioned in the ß face of the estrone moiety, with an O-C-C-C torsion angle of 44.1 (5)°, and the carbonyl bond length of the hormone moiety is 1.216 (5) Å, typical of a C=O double bond. The average Fe-C bond length of the substituted Cp ring [Fe-C(Cp*)] is similar to that of the unsubstituted one [Fe-C(Cp)], i.e. 2.048 (3) versus 2.040 (12) Å. The structure of the complex is compared with those of estrone and eth-oxy-methyl-estrone.

RESUMO

Four new platinum(II) complexes, namely tetra-ethyl-ammonium tri-bromido-(2-methyl-1,3-benzo-thia-zole-κN)platinate(II), [NEt4][PtBr3(C8H7NS)] (1), tetra-ethyl-ammonium tri-bromido-(6-meth-oxy-2-methyl-1,3-benzo-thia-zole-κN)platinate(II), [NEt4][PtBr3(C9H9NOS)] (2), tetra-ethyl-ammonium tri-bromido-(2,5,6-trimethyl-1,3-benzo-thia-zole-κN)platinate(II), [NEt4][PtBr3(C10H11NS)] (3), and tetra-ethyl-ammonium tri-bromido-(2-methyl-5-nitro-1,3-benzo-thia-zole-κN)platinate(II), [NEt4][PtBr3(C8H6N2O2S)] (4), have been synthesized and structurally characterized by single-crystal X-ray diffraction techniques. These species are precursors of compounds with potential application in cancer chemotherapy. All four platinum(II) complexes adopt the expected square-planar coordination geometry, and the benzo-thia-zole ligand is engaged in bonding to the metal atom through the imine N atom (Pt-N). The Pt-N bond lengths are normal: 2.035 (5), 2.025 (4), 2.027 (5) and 2.041 (4) Šfor complexes 1, 2, 3 and 4, respectively. The benzo-thia-zole ligands are positioned out of the square plane, with dihedral angles ranging from 76.4 (4) to 88.1 (4)°. The NEt4 cation in 3 is disordered with 0.57/0.43 occupancies.