RESUMO
Novel lipophilic platinum(II) complexes (LSPt-1-3), containing 3,5-diisopropylsalicylate (DIPS) as a leaving group and 2NH(3) or 1R,2R-diaminocyclohexane or (4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane as the carrier, have been synthesized, characterized and evaluated in vitro and in vivo. The octanol/water distribution coefficient of the complexes has also been measured. The results showed that the complexes achieved a typical square planar and the octanol/water distribution coefficient logP was 4.27, 4.37 and 4.31. The complexes were tested by SRB method to be more cytotoxic than Carboplatin, Oxaliplatin and Eptaplatin against 3AO, A549, NCI-H460 and SGC-7901 human cancer cell lines. Among complexes, LSPt-2 was much more effective than Carboplatin and Oxaliplatin in treating the NCI-H460 non-small-cell lung tumor-bearing mice. Its optimal activity was 38.8% (T/C) at a dose of 30 mg/kg following i.p. administration. LD(50) for the complex was found to be 230.9 mg/kg. LSPt-2 exhibited great anticancer activity, good lipophilic ability and low toxicity and therefore, it is a promising candidate for effective and stable pharmaceutical liposomal platinum anticancer drug.
Assuntos
Compostos de Platina/síntese química , Compostos de Platina/farmacologia , Salicilatos/química , Animais , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Dose Letal Mediana , Espectroscopia de Ressonância Magnética , Camundongos , Compostos de Platina/química , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Espectrofotometria UltravioletaRESUMO
A novel mixed NH(3)/NH(2)OH platinum(II) complex cis-[Pt(NH(3))(NH(2)OH)Cl(2)] was synthesized and characterized by elemental analysis, FAB-MS, FT-IR and (1)H NMR spectroscopy. This complex was determined to have a good water-solubility and satisfactory stability. The pertinent complex was evaluated for its in vitro cytotoxicity against 3AO, HCT-116, LNcap, A549/ATCC and SGC-7901 human carcinoma cell lines. It shows appreciable cytotoxic activity that is comparable with cisplatin and is much more active than carboplatin.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Cisplatino/análogos & derivados , Hidroxilaminas/química , Antineoplásicos/química , Linhagem Celular Tumoral , Cisplatino/síntese química , Cisplatino/química , Cisplatino/farmacologia , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Estabilidade de Medicamentos , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Solubilidade , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Diiodo-, dibromo- and dichloro-platinum(II) complexes containing L-histidine ligand were prepared. Their spectra and X-ray crystal structure of the dibromo-platinum(II) complex were described. Only the dichloro-platinum(II) complex showed comparable cytotoxic activity with carboplatin against A549/ATCC, HT-29, and LNcap cell lines. Nevertheless the complexes with COOH-substituted ligands histidine may be good starting materials to synthesize targeting platinum complexes since they could be easily linked to suitable carrier molecules via esterification.
Assuntos
Antineoplásicos/síntese química , Histidina/química , Compostos Organoplatínicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligantes , Modelos Moleculares , Estrutura Molecular , Compostos Organoplatínicos/química , Compostos Organoplatínicos/farmacologiaRESUMO
A series of novel platinum(II) complexes involving a physiologically active carrier histamine as the carrier, cis-[Pt(histamine)X2] (X2=2Cl-, oxalate, malonate, 1,1-cyclobutanedicarboxylate (CBDCA), 3-hydroxy-1,1-cyclobutanedicarboxylate (HO-CBDCA)), have been synthesized and characterized by elemental analysis and spectroscopic data along with X-ray crystal structure for a representative complex cis-[Pt(histamine)Cl2]. The cytotoxicity of the complexes has also been assessed in the human cancer cell lines A549/ATCC, HT-29, and LNcap. One complex, cis-[Pt(histamine)Cl2], is more active than carboplatin against both the sensitive and resistant cells.
Assuntos
Antineoplásicos/farmacologia , Quelantes/química , Histamina/análogos & derivados , Histamina/química , Compostos Organoplatínicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Cristalografia por Raios X , Resistencia a Medicamentos Antineoplásicos , Histamina/síntese química , Histamina/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/química , Relação Estrutura-AtividadeRESUMO
Four diam(m)ineplatinum(II) complexes containing beta-phenylisosuccinate as the leaving groups were prepared, characterized, and evaluated for their cytotoxicity against A549/ATCC human lung cancer cell line and SGC-7901 human gastric cancer cell line. One of the complexes, (trans-1R,2R-diaminocyclohexane)-beta-phenylisosuccinatoplatinum(II) 4, was much more active than cisplatin and carboplatin.
Assuntos
Antineoplásicos , Cisplatino/análogos & derivados , Compostos Organoplatínicos , Succinatos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Desenho de Fármacos , Humanos , Isomerismo , Ligantes , Estrutura Molecular , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/química , Compostos Organoplatínicos/farmacocinéticaRESUMO
Novel lipophilic (diamine)platinum(II) complexes of salicylate derivatives as the leaving groups were synthesized and characterized by elemental analysis, FAB(+)-MS, FT-IR, and (1)H NMR spectroscopy. Most of the resulting platinum complexes had high solubility in organic solvents such as ethanol, acetone, and ether, and had right partition coefficient suited to be encapsulated in liposomes. The pertinent complexes were evaluated for their in vitro cytotoxicity against A549 human lung carcinoma and SGC-7901 human gastric carcinoma cell lines. They showed better cytotoxic activity than carboplatin and oxaliplatin.