RESUMO
Four new platinum(II) complexes of 3-aminocyclopentanespiro-5-hydantoin (acpsh) and 3-aminocycloheptanespiro-5-hydantoin (achpsh) were synthesized and characterized by elemental analysis, IR and 1NMR spectra. The spectral analyses indicated a cis-square planar structure of the complexes with ligands coordinated via the NH2 group. The complexes were evaluated for in vitro cytotoxicity in murine erythroleukemia (MEL) cells, clone F4N, using cell-growth and macromolecular synthesis assay. The compounds, with exception of [Pt(NH3)(achpsh)Cl2] (IV), exhibited much lower cytotoxicity than that of cisplatin (DDP). Compound IV was nearly as cytotoxic as DDP. The new complexes exerted low antibacterial activity as assessed by seven bacterial strains.
Assuntos
Antibacterianos/síntese química , Antineoplásicos/síntese química , Sobrevivência Celular/efeitos dos fármacos , Hidantoínas/química , Compostos Organoplatínicos/síntese química , Compostos de Espiro/síntese química , Animais , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , Linhagem Celular , Replicação do DNA/efeitos dos fármacos , Hidantoínas/farmacologia , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Compostos Organoplatínicos/farmacologia , Espectrofotometria Infravermelho , Compostos de Espiro/farmacologiaRESUMO
New platinum(II) complexes of 3-aminocyclohexanespiro-5-hydantoin (achsh) were prepared and characterized. Ab initio calculation of the structure and the measurements of IR and NMR spectra of [Pt(NH(3))(achsh)Cl(2)] were also performed. Quantum-chemical and spectroscopic studies indicated a cis-square planar structure with a hydantoin ligand coordinated via the NH(2) group. The complexes were evaluated for in vitro cytotoxicity in murine erythroleukemia (MEL) cells, clone F4N, as well as for in vivo antitumor activity toward murine L1210 leukemia. The complexes exerted significantly lower in vitro and in vivo toxicities compared with those of cisplatin (cis-diamminedichloroplatinum(II), DDP). The complex [Pt(NH(3))(achsh)Cl(2)] exhibited antitumor activity against L1210 leukemia, comparable to that of cisplatin, resulting at a dose of 72 mg/kg in a %T/C (increased survival time) of 191%. This complex, as well as cisplatin, induced apoptosis in F4N cells, and exerted antibacterial activity as assessed in 10 bacterial strains.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , Hidantoínas/síntese química , Hidantoínas/farmacologia , Compostos Organoplatínicos/química , Compostos de Platina/síntese química , Compostos de Platina/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/toxicidade , Antineoplásicos/química , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Hidantoínas/química , Hidantoínas/toxicidade , Espectroscopia de Ressonância Magnética , Camundongos , Modelos Moleculares , Conformação Molecular , Transplante de Neoplasias , Compostos Organoplatínicos/toxicidade , Compostos de Platina/química , Compostos de Platina/toxicidade , Espectrofotometria Infravermelho , Células Tumorais CultivadasRESUMO
3-Aminocycloalkanespiro-5-hydantoins were synthesized and their biological activity was studied. In contrast to hydantoins, these compounds failed to induce either anticonvulsive effects in the central nervous system or inhibitory effects on cholinergic contractions in the enteric nervous system. However, they exerted well pronounced, atropinsensitive, contractile effects on the guinea-pig ileum longitudinal muscle preparations. Structure-activity relationships established allow the assumption that: (i) the reduction of the ring size in the molecule of the spirohydantoins leads to an increase in the potency of the respective analogue to induce contractile effect; (ii) the introduction of -NH2 in position 3 increases the ability of all the compounds studied to exert contractions; (iii) the enlargement of the ring leads to: (1) an increase of the degree of desensitization of the preparations; and (2) a decrease (except 1a) of the potency of the analogues to exert contractile effects.
