RESUMO
A previous study showed that intravenous immunoglobulin (IVIG) could preserve higher levels of biologically active lactone moieties of topotecan, 7-ethyl-10-hydroxycamptothecin (SN-38) and 10-hydroxycamptothecin at physiological pH 7.40. As one of camptothecin analogues (CPTs), the interaction of 7-ethylcamptothecin and IVIG was studied in vitro in this study. It was shown that the main binding mode of IVIG to 7-ethylcamptothecin was hydrophobic interaction and hydrogen bonding, which is a non-specific and spontaneous interaction. The hydrophobic antigen-binding cavity of IgG would enwrap the drug into a host-guest inclusion complex and prevent hydrolysis of the encapsulated drug, while the drug is adjacent to the chromophores of IgG and may exchange energy with chromophores and quench the fluorescence of the protein. Also, the typical ß-sheet structure of IVIG unfolded partially after binding to 7-ethylcamptothecin. Additionally, the binding properties of IVIG and six CPTs with different substituents at A-ring and/or B-ring including camptothecin, topotecan, irinotecan, 10-hydroxycamptothecin, 7-ethylcamptothecin and SN-38 were collected together and compared each other. Synergizing with anti-cancer drugs, IVIG could be used as a transporter protein for 7-ethylcamptothecin and other CPTs, allowing clinicians to devise new treatment protocols for patients.
Assuntos
Camptotecina/análogos & derivados , Imunoglobulinas Intravenosas/química , Camptotecina/química , Camptotecina/metabolismo , Humanos , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Imunoglobulina G/química , Imunoglobulina G/metabolismo , Imunoglobulinas Intravenosas/metabolismo , Imunoglobulinas Intravenosas/farmacocinética , Cinética , Modelos Moleculares , Conformação Molecular , Ligação Proteica , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , TermodinâmicaRESUMO
To investigate the effects of gambognic acid (GA) on TRAIL-induced apoptosis of cancer cells, human colon HT-29 cancer cells were treated with GA to promote apoptosis. Inhibition of the cell proliferation was measured with MTT assay and cell apoptosis was detected with formation of DNA ladders in agarose gel electrophoresis, and activation of caspase activity. The content of cytosolic reactive oxygen species (ROS) was measured with flow cytometry. The activities of Caspase-3, -8, -9 were detected using spectrophotometric assay. The levels of c-FLIP, CHOP, DR4 and DR5 in cells were tested by Western blot. Combination of GA (1 µg · mL(-1)) and TRAIL (40 ng · mL(-1)) significantly reduced proliferation and increased apoptosis of HT-29 cells over those induced by each agent alone. Percentage of apoptotic cells was increased to 45.5%. GA markedly enhanced the intracellular ROS generation. Expression of CHOP, DR4 and DR5 was up-regulated to 7.38, 5.41, and 4.85 times of the control group, respectively. GA promoted activation of Caspase-3, -8, and -9 by TRAIL (P<0.05). Furthermore, the expression of anti-apoptotic protein c-FLIP was down-regulated to 0.22 ± 0.08 times of the control group. In conclusion, GA sensitizes HT-29 cells to TRAIL-induced apoptosis by promoting ROS-activated ERS pathways, up-regulating of DR4 and DR5, and inhibiting c-FLIP expression.
Assuntos
Apoptose , Neoplasias do Colo/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Xantonas/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Caspases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Células HT29 , Humanos , Espécies Reativas de Oxigênio/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Both tribendimidine and mebendazole are broad-spectrum drugs for anti-intestinal nematodes. We aim to assess the efficacy and safety of tribendimidine and mebendazole in patients with co-infection of Clonorchis sinensis and other helminths. METHOD: We performed a randomized open-label trial in Qiyang, People's Republic of China. Eligible participants were randomly assigned to one of four groups: (i) a single dose of 400 mg tribendimidine, (ii) 200 mg tribendimidine twice daily, (iii) 75 mg/kg praziquantel divided in four doses within 2 days, and (iv) a single dose of 400 mg mebendazole. Cure rates and egg reduction rates were assessed, and adverse events were monitored after treatments. Uncured patients accepted the second treatment with the same drugs after the first treatment. RESULTS: 156 patients were eligible for the study. Results from the first treatment showed that the cure rates of single-dose tribendimidine and praziquantel against C. sinensis were 50% and 56.8%, respectively; the single-dose tribendimidine achieved the cure rate of 77.8% in the treatment for hookworm, which was significantly higher than that of praziquantel; Low cure rates were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura (28.6% and 23.1%). Results of the second treatment illustrated the cure rates of tribendimidine and praziquantel against C. sinensis were 78.1% and 75%, respectively. Most adverse events were mild and transient. Adverse events caused by tribendimidine were significantly less than praziquantel. CONCLUSION: Single-dose tribendimidine showed similar efficacy against C. sinensis as praziquantel with less adverse events, and achieved significantly higher cure rate in the treatment for hookworm than those of praziquantel and mebendazole. Low cure rates, which were still higher than other drugs, were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN55086560.
Assuntos
Anti-Helmínticos/uso terapêutico , Clonorquíase/tratamento farmacológico , Coinfecção/tratamento farmacológico , Helmintíase/tratamento farmacológico , Mebendazol/uso terapêutico , Fenilenodiaminas/uso terapêutico , Praziquantel/uso terapêutico , Adulto , Animais , Ascaríase/tratamento farmacológico , Feminino , Humanos , Masculino , Mebendazol/efeitos adversos , Pessoa de Meia-Idade , Fenilenodiaminas/efeitos adversos , Praziquantel/efeitos adversosRESUMO
OBJECTIVE: To understand the cross-resistance of Culex pipiens pallens to common pesticides, so as to provide the evidence for improving the application of chemical pesticides. METHODS: The IV instar larvae of DDVP-resistant, propoxur-resistant and cypermethrin-resistant strains as well as the sensitive strain of Culex pipiens pallens were collected to detect the resistance to DDVP, propoxur and cypermethrin based on the WHO bioassay method. RESULTS: The resistance coefficients of DDVP-resistant strain to DDVP, propoxur and cypermethrin were 14.47, 8.96 and 207.27 respectively. The resistance coefficients of propoxur-resistant strain to DDVP, propoxur and cypermethrin were 3.27, 6.93 and 8.65 respectively. The resistance coefficients of cypermethrin-resistant strain to DDVP, propoxur and cypermethrin were 2.93, 1.61 and 501.11 respectively. CONCLUSION: The resistance and cross-resistance could be generated during the long-term application of a single kind of chemical pesticide, and we should pay more attention to the varieties and dosages of them.
Assuntos
Culex/efeitos dos fármacos , Resistência a Inseticidas , Inseticidas/farmacologia , Animais , Culex/crescimento & desenvolvimento , Larva/efeitos dos fármacos , Testes de Sensibilidade ParasitáriaRESUMO
The Er(III) complexes are prepared from Er(NO(3))(3).6H(2)O and Schiff-base ligands derived from 8-hydroxyquinoline-2-carboxaldehyde with four aroylhydrazines, including benzoylhydrazine, 2-hydroxybenzoylhydrazine, 4-hydroxybenzoylhydrazine and isonicotinylhydrazine, respectively. X-ray crystal and other structural analyses indicate that Er(III) and every ligand can form a binuclear Er(III) complex with nine-coordination and 1: 1 metal-to-ligand stoichiometry at the Er(III) centre. All the Er(III) complexes can bind to calf thymus DNA through intercalation with the binding constants at the order of magnitude 10(6) M(-1), and they may be used as potential anticancer drugs. All the Er(III) complexes have strong scavenging effects for hydroxyl radicals and superoxide radicals; however, complex containing active phenolic hydroxyl group shows stronger scavenging effects for hydroxyl radicals and complex containing N-heteroaromatic substituent shows stronger scavenging effects for superoxide radicals.
Assuntos
Aldeídos/química , Complexos de Coordenação/química , DNA/metabolismo , Érbio , Hidrazinas/química , Oxiquinolina/análogos & derivados , Oxiquinolina/química , Bases de Schiff/química , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Bovinos , Complexos de Coordenação/metabolismo , Cristalografia por Raios X , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/metabolismo , Hidroxibenzoatos/química , Ligantes , Estrutura Molecular , OxirreduçãoRESUMO
X-ray crystal and other structural analyses indicate that Dy(III) and every ligand can form a binuclear Dy(III) complex with nine-coordination and 1:1 metal-to-ligand stoichiometry at the Dy(III) center. All the ligands and Dy(III) complexes can bind to Calf thymus DNA through intercalations with the binding constants at the order of magnitude 10(5)-10(7) M(-1), but Dy(III) complexes present stronger affinities to DNA than ligands. All the ligands and Dy(III) complexes can be used as potential anticancer drugs. All the ligands and Dy(III) complexes have strong scavenging effects for hydroxyl radicals and superoxide radicals but complex containing active phenolic hydroxyl group shows stronger scavenging effects for hydroxyl radicals and complex containing N-heteroaromatic substituent shows stronger scavenging effects for superoxide radicals.
Assuntos
Antioxidantes/química , Cicloexenos/química , DNA/química , DNA/metabolismo , Disprósio/química , Hidrazinas/química , Compostos Organometálicos/química , Oxiquinolina/química , Bases de Schiff/química , Animais , Antioxidantes/metabolismo , Bovinos , Cristalografia por Raios X , DNA/efeitos dos fármacos , Ligantes , Estrutura Molecular , Oxirredução , Timo/químicaRESUMO
Eu(III) and every newly synthesized ligand can form a binuclear Eu(III) complex with a 1:1 metal to ligand stoichiometry and nine-coordinate at Eu(III) center. Every ligand acts as a dibasic tetradentate ligand, binding to Eu(III) through the phenolate oxygen atom, nitrogen atom of quinolinato unit, the C=N group (methylene) and (-)O-C=N- group (enolized and deprotonated from O=C-NH- group) of the aroylhydrazine side chain. One DMF (N,N-dimethylformamide) molecule is binding orthogonally to the ligand-plane from one side to the metal ion, while another DMF and a nitrate anion (bidentate) are binding from the other. Dimerization of the monomeric unit occurs through the phenolate oxygen atoms leading to a central planar four-membered (EuO)(2) ring. On the other hand, all the ligands and Eu(III) complexes may be used as potential anticancer drugs, binding to Calf thymus DNA through intercalations at the order of magnitude 10(5)-10(7) M(-1). All the ligands and Eu(III) complexes are strong scavengers of hydroxyl radicals and superoxide radicals, but Eu(III) complex containing active phenolic hydroxyl group shows stronger scavenging effects for hydroxyl radicals than others, and Eu(III) complex containing N-heteroaromatic substituent shows stronger scavenging effects for superoxide radicals than others.
Assuntos
DNA/química , Európio/química , Hidrazinas/química , Compostos Organometálicos/química , Oxiquinolina/química , Animais , Antioxidantes/química , Bovinos , Cristalografia por Raios X , Ligantes , Estrutura Molecular , Bases de Schiff/química , Superóxidos/químicaRESUMO
X-ray crystal and other structural analyses indicate that Yb(III) and all four newly synthesized ligands can form a binuclear Yb(III) complex with a 1:1 metal to ligand stoichiometry by octacoordination at the Yb(III) center. Investigations of DNA binding properties show that all the ligands and Yb(III) complexes can bind to Calf thymus DNA through intercalations with the binding constants at the order of magnitude 10(5)-10(7) M(-1), but Yb(III) complexes present stronger affinities to DNA than ligands. All the ligands and Yb(III) complexes may be used as potential anticancer drugs. Investigations of antioxidation properties show that all the ligands and Yb(III) complexes have strong scavenging effects for hydroxyl radicals and superoxide radicals but Yb(III) complexes show stronger scavenging effects for hydroxyl radicals than ligands.
Assuntos
Antioxidantes/química , Cristalografia por Raios X/métodos , DNA/química , Hidrazonas/química , Bases de Schiff/química , Itérbio/química , Animais , Humanos , Modelos Moleculares , Estrutura Molecular , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , ViscosidadeRESUMO
A novel Schiff base ligand (L = 7-methoxychromone-3-carbaldehyde benzoyl hydrazone) and its La(III) and Eu(III) complexes have been successfully prepared. The crystal structure of [LaL(2)(NO(3))(3)].H(2)O was characterized by X-ray crystallography. It crystallizes in monoclinic, space group C2/c with crystallographic data: a = 27.7173(17) A, b = 10.0002(6) A, c = 14.7884(9) A, beta = 102.6870(10) degrees and Z = 4. In the structure, the La(III) ion satisfies 12 coordination and three nitrate coordinate as bidentate ligand. The biological experiments show that the ligand and its two complexes can strongly bind to DNA through intercalation mode, and the three compounds also exhibit good antioxidant activities against OH(*) and O(2) (-*). Moreover, it is found that the Eu(III) complex exhibits characteristic fluorescence of europium ion in different organic solvent.