Antiretroviral activity of thiosemicarbazone metal complexes

Thiosemicarbazones display a wide antimicrobial activity by targeting bacteria, fungi, and viruses. Here, we report our studies on the antiviral activity of two thiosemicarbazone metal complexes, [bis(citronellalthiosemicarbazonato)nickel(II)] and [aqua(pyridoxalthiosemicarbazonato)copper(II)] chloride monohydrate, against the retroviruses HIV-1 and HTLV-1/-2. Both compounds exhibit antiviral properties against HIV but not against HTLVs . In particular, the copper complex shows the most potent anti-HIV activity by acting at the post-entry steps of the viral cycle.     

金属细菌叶绿素的合成及其对肿瘤细胞的抑制作用金属细菌叶绿素的合成及其对肿瘤细胞的抑制作用

目的寻找一种新型光动力学疗法光敏剂。方法采用从光合细菌中分离纯化的脱镁细菌叶绿素为配体，与金属盐在有机溶剂中反应，合成了Cu，Zn，Co，Ni 4种金属细菌叶绿素，并对其紫外可见光谱和荧光光谱进行研究。此外还研究了4种金属细菌叶绿素对K562和HL60两种白血病细胞生长的影响。结果4种金属细菌叶绿素的光谱图都有可预见的漂移，证明金属已配位到细菌叶绿素的卟啉大环上。同时，4种金属细菌叶绿素都有很强的抑瘤作用，光照可以明显提高其抑瘤率。结论金属细菌叶绿素作为一种新型光敏剂具有优良的性质，是新一代光敏剂发展的一个方向。     

Ovarian cancer activity of cyclic amine and thiaether metal complexes

A thiaether metal complex 1-aza-4,7-dithiacyclononane-RhCl3, 2, and cyclic amine metal complexes tacn-CuBr2, 3, and Me3tacn-RuCl3, 4, have been evaluated for anticancer activity against the ovarian cancer cell line NuTu-19 and for cell toxicity against the noncancerous ovarian tissue cell line OVepi. Specifically, metal complex 2 is active when compared to cisplatin at micromolar concentrations using the MTT and cell invasion assay. The in vitro results reported warrant further evaluation of metal complex 2 in living systems.     

半乳糖胺-过渡金属配合物的合成,结构表征和活性研究Δ

目的半乳糖糖胺-过渡金属配合物的合成及其水解酶活性的研究。方法以半乳糖为原料,经三(2-氨乙基)胺连接修饰后再分别与过渡金属Cu(II)、Ni(II)反应合成两个配合物。以对硝基苯酚吡啶甲酸酯(PNPP)为水解模拟酶模型,研究了在两个不同pH值下所合成糖胺-过渡金属配合物的水解活性。结果通过元素分析、金属含量测定、光谱分析及摩尔电导等表征手段,确定了两个配合物化学结构为[C24H48N4O15CuCl]Cl·3H2O]和[C24H48N4O15Ni·2H2O]Cl2·H2O],而且两个配合物的水解速率远大于自发水解的速率。结论三角双锥构型的Cu(II)配合物和具有八面体构型的Ni(II)配合物都具有较好的金属水解酶活性。     

磺酰脲衍生物金属配合物的降血糖作用研究

目的：对10个磺酰脲衍生物金属配合物的降血糖作用进行初步筛选。方法：正常小鼠灌胃给药后,剪尾取血,用葡萄糖氧化酶-过氧化物酶（GOD-PAP）法测定血糖,以甲苯磺丁脲（D860）作为阳性对照药物,分析它们的降血糖作用,探讨其作用机理及化学结构与降血糖作用的构效关系。结果：实验表明,ZnL2.2H2O、NdL3.2H2O、SmL3.2H2O、Zn（HL＇）2.2NO3、Eu（HL＇）3.3NO3、HL、HL＇等7个化合物,均具有降低正常小鼠血糖的活性,而EuL3.2H2O、Nd（HL＇）3.3NO3、Sm（HL＇）3.3NO3降糖活性不明显。结论：HL在2h对正常小鼠的降血糖活性强于D860,提示对甲苯磺酰脲1位取代基为脂环基（环己基）时,其降血糖活性高于直链脂基（丁基）,更高于杂环基团（4-安替比林基）。     

Synthesis,characterization antibacterial and antifungal activity of some transition metal complexes

Some new transition metal complexes with monomethyl succinate are reported. Several physical techniques, such as elemental analysis and melting point, and in addition various spectroscopic techniques including ¹H-, ¹³C-NMR and UV/visible and infrared spectroscopy were used to study the chemical structure of the prepared complexes. The octahedral geometry is proposed on the basis of these spectral techniques. The synthesized complexes were also exposed to various bacteria and fungi to establish their bioactivities.     

Antimycobacterial activity of fusaric acid from a mangrove endophyte and its metal complexes

Due to the increasing prevalence of multidrug-resistant Mycobacterium tuberculosis, there is an urgent need for new antituberculosis drugs that have novel mechanisms of action. As part of our ongoing search for antimycobacterial metabolites from mangrove endophytes, chemical analysis of the active extract of a strain of Fusarium sp. was performed, which led to the isolation of fusaric acid as the predominant constituent. A variety of metal complexes of fusaric acid were prepared. Antimycobacterial assays showed that Cadmium (II) and Copper (II) complexes exhibited potent inhibitory activity against the M. bovis BCG strain [minimum inhibitory concentration (MIC) = 4 μg/mL] and the M. tuberculosis H37Rv strain (MIC = 10 μg/mL), respectively. This is the first report of the antimycobacterial activity of the mangrove Fusarium metabolite and its coordinating metal complexes.     

Synthesis, analysis and in vitro antibacterial activity of new metal complexes of sulbactam

Complexes of copper(II), nickel(II) and iron(III) with beta-lactamase inhibitor sulbactam have been synthesized, characterized and identified by elemental analysis, IR and 1H NMR spectroscopy. These complexes have been then tested for their in vitro antibacterial activity in combination with ampicillin against various bacterial species.     

Synthesis,characterization and biological activity of some unsymmetrical Schiff base transition metal complexes

In this study, several unsymmetrical Schiff bases and their cobalt and manganese complexes have been synthesized and characterized. The unsymmetrical Schiff bases were prepared from reaction of o-phenylendiamine derivatives with 1-hydroxy-2-acetonaphthone and then the product was reacted with the following aldehydes: salicyaldehyde, 2-hydroxynaphthaldehyde, 2-pyridinecarboxaldehyde and 2-qinolinecarboxaldehyde to produce the desired tetradentate unsymmetrical Schiff base ligands H2SL, H2NL, HPYL and HQN, respectively. Reaction of these ligands with cobalt and manganese salts produced complexes of the general formula [M(SL)], [(NL)], [M(PYL)] and [M(QL)]. All the complexes were characterized by elemental analysis, infrared spectroscopy, UV-visible spectroscopy, electrical conductivity and magnetic susceptibility measurements. The prepared complexes were examined for their anti-bacterial activity using gram-positive and gram-negative pathogens. The following complexes showed strong antibacterial activity against Staphylococcus aureus: MnSL1, MnSL2 and MnSL3. The genotoxic activity of four complexes, which are MnNL1, MnSL1, CoNL1 and CoSL1, were examined using 8-hydroxy-2-deoxy guanosine (8-OHdG) assay in cultured human blood lymphocytes. All examined complexes were found to be genotoxic at examined concentrations (0.1–100?µg/mL), but with variable magnitudes (p?<?0.05). The levels of 8-OHdG induced by MnNL1 and MnSL1 were significantly higher than that induced by CoNL1 and CoSL1 ones. In general, the order of mutagenicity of the compounds is MnSL1?>?MnNL1?>?CoSL1?>?CoNL1. In conclusion, some of the prepared complexes showed some biological activities that might be of interest for future research.     

Antimalarial multidentate metal complexes

This patent from the University of Washington describes the synthesis and application of novel multidentate cationic metal complexes. Activity against drug-resistant Plasmodium falciparum is demonstrated. The complexes may also have applications in the treatment of cancer and as delivery systems for the specific targeting of active pharmacophores, although no direct evidence is presented for the latter. No compounds are specifically claimed, but [N,N′-bis[3-(2-hydroxy-4,6-dimethoxy-benzyl-amino)propyl]ethylene diamine] Fe(III) complex showed an IC50 of 1.0 - 1.5 μM against both chloroquine-sensitive HB3 and chloroquine-resistant FCR-3, Indo-1 and Dd2 strains of P. falciparum.     

New metal complexes of 4-methyl-7-hydroxycoumarin sodium salt and their pharmacological activity.

Complexes of copper (II), zinc (II), nickel (II), cobalt (II) and iron (III) with 4-methyl-7-hydroxycoumarin sodium salt (Mendiaxon, Hymecromone) were synthesized by mixing of equimolar amounts of the respective metal nitrates and 4-methyl-7-hydroxycoumarin sodium salt in water. The complexes were characterized and identified by elemental analysis, conductivities, IR, 1H NMR spectroscopy and mass spectral data. DTA and TGA have been applied to study the compositions of the compounds. Thermal analysis of the complexes indicate the formation of compounds which correspond to the compositions Met(HL)2 x nH2O, where Met = Cu, Zn, Ni, Co; n = 2, 3 or 4 and Fe(HL)3 x 5H2O. The newly synthesized compounds were assayed for acute intraperitoneal and per oral toxicity, influence on blood clotting time and the most active complex was investigated for spasmolytic activity.     

Synthesis and antimetastatic activity of metal complexes based on substituted pyridinecarboxylic acid amides and platinum tetrachloride

Previously unreported platinum tetrachloride derivatives have been synthesized via the interaction between dipotassium- and disodiumhexachloroplatinates with substituted amides of nicotinic and isonicotinic acid. The synthesized compounds exhibit low general toxicity and show high antimetastatic activity with respect to experimental melanoma B-16 and Lewis lung carcinoma strains. Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 43, No. 3, pp. 12 – 16, March, 2009.     

Comparison of antibacterial activity of a new cephalosporin, ceftizoxime (FK 749) with other cephalosporin antibiotics.

FK 749 is a distinctive new parenteral cephalosporin antibiotic with a broad antibacterial spectrum which is more potently active against a wide variety of Gram-negative bacilli, including the opportunistic pathogens such as Citrobacter and Enterobacter species and Serratia marcescens, than SCE 963, T 1551 and cefmetazole. The activity of FK 749 against Escherichia coli, Klebsiella pneumoniae, pyogenes was by far superior to that of the three other antibiotics. These test organisms were not resistant to FK 749. The antibacterial activity of FK 749 against Pseudomonas aeruginosa was almost the same as that of ticarcillin but was inferior to that of gentamicin and T 1551. The bactericidal activity of FK 749 against E. coli, K. pneumoniae and Proteus mirabilis was more potent than that of the three other antibiotics. FK 749, like cefmetazole, was extremely stable to beta-lactamases. In studies in mice, the therapeutic effect of subcutaneous injection of FK 749 against various infections due to Gram-negative bacilli was by far superior to that of SCE 963, T 1551 and cefmetazole, was almost the same as that of SCE 963 and cefmetazole against Staphylococcus aureus infection and that of ticarcillin against P. aeruginosa infection.     

Pharmacokinetics and pharmacodynamics of ceftobiprole, an anti-MRSA cephalosporin with broad-spectrum activity

Ceftobiprole, a beta-lactam, is the first of a new generation of broad-spectrum cephalosporins in late-stage development with activity against methicillin-resistant Staphylococcus aureus (MRSA) in addition to broad-spectrum bactericidal activity against other Gram-positive and Gram-negative pathogens. The prodrug, ceftobiprole medocaril, is converted rapidly and almost completely to the active drug, ceftobiprole, upon infusion by type A esterases. In humans, ceftobiprole binds minimally (16%) to plasma proteins, and binding is independent of the drug and protein concentrations. Its steady-state volume of distribution (18.4 L) approximates the extracellular fluid volume in humans. Ceftobiprole undergoes minimal hepatic metabolism, and the primary metabolite is the beta-lactam ring-opened hydrolysis product (open-ring metabolite). Systemic exposure of the open-ring metabolite accounts for 4% of ceftobiprole exposure following single-dose administration; approximately 5% of the dose is excreted in the urine as the metabolite. Ceftobiprole does not significantly induce or inhibit relevant cytochrome P450 enzymes and is neither a substrate nor an inhibitor of P-glycoprotein. Ceftobiprole is rapidly eliminated, primarily unchanged, by renal excretion, with a terminal elimination half-life of 3 hours; the predominant mechanism responsible for elimination is glomerular filtration, with approximately 89% of the dose being excreted as the prodrug, active drug (ceftobiprole) and open-ring metabolite. The pharmacokinetics of ceftobiprole are linear following single and multiple infusions of 125-1000 mg. Steady-state drug concentrations are attained on the first day of dosing, with no appreciable accumulation when administered three times daily (every 8 hours) and twice daily (every 12 hours) in subjects with normal renal function. Low intersubject variability has been seen across studies. Ceftobiprole exposure is slightly higher (~15%) in females than in males; this difference has been attributed to bodyweight. However, the pharmacodynamics of ceftobiprole are similar in males and females, and dosing adjustments are not required based on gender. In patients with moderate to severe renal impairment, systemic clearance of ceftobiprole correlated well with creatinine clearance. For these patients, dose adjustments for the treatment of infections caused by target pathogens, including MRSA, should be based on creatinine clearance. Ceftobiprole is undergoing clinical evaluation in phase III trials in patients with complicated skin and skin structure infections, patients with nosocomial pneumonia, and community-acquired pneumonia in hospitalized patients.     

新头孢菌素衍生物的定量构效关系研究

目的　研究一类新合成的抗流感嗜血杆菌头孢菌素衍生物的定量构效关系。方法　应用半经验量子化学方法和误差反向传播人工神经网络的方法。结果　系统计算了4 8个头孢菌素类化合物的1 8个分子描述符,从中筛选出7个描述符。随机挑选4 3个化合物作为训练样本集,5个化合物作为测试样本集,检验结果表明模型具有较高的精度(检验样本最大相对误差小于5 %)。结论　头孢菌素化合物的LUMO能量、疏水性、C8原子及C3 位取代基的净电荷是影响其抗菌活性的主要因素,所建立的定量构效关系模型能够有效地进行体外抗流感嗜血杆菌活性与头孢菌素类化合物分子描述符的相关性分析。     

Antibacterial activity of BMY-28142, a novel broad-spectrum cephalosporin

BMY-28142, 7-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3- (1-methylpyrrolidinio)methyl-3-cephem-4-carboxylate, exhibited a well-balanced, extended-spectrum of antibacterial activity both in vitro and in vivo. Against Staphylococci and Streptococci, BMY-28142 was about four to ten times more active than ceftazidime and comparable to cefotaxime. Most Enterobacteriaceae were more susceptible to BMY-28142 than to ceftazidime, though strains of Pseudomonas aeruginosa were slightly more sensitive to ceftazidime. BMY-28142 showed potent activity against Gram-negative bacteria resistant to ceftazidime and/or cefotaxime. Bactericidal activity of BMY-28142 against 10 strains of P. aeruginosa was superior to that of ceftazidime. In bacterial infection models in mice, BMY-28142 was more effective than ceftazidime against three Gram-positive and three Gram-negative pathogens. The anti-pseudomonal in vivo activity of BMY-28142 was nearly comparable to that of ceftazidime. The blood levels and urinary excretion rates of BMY-28142 in mice were similar to those of ceftazidime.     

Cytotoxic activity of metal complexes of biogenic polyamines: polynuclear platinum(II) chelates

Several polynuclear Pt(II) chelates with biogenic polyamines were synthesized and screened for their potential antiproliferative and cytotoxic activity in different human cancer cell lines. To gather information regarding the structure-activity relationships underlying their biological activity, the complexes studied were designed to differ in geometrical parameters such as the nature of the ligand and the number and chemical environment of the metal centers. Distinct effects were found for different cell lines and different structural characteristics of the complexes; chelates II, III, and IV displayed specificity toward the HeLa and HSC-3 epithelial-type cells, while V, VI, and VII were clearly more effective against the THP-1, MOLT-3, and CCRF-CEM leukemia cell lines. The toxicity of these Pt(II) complexes on noncancer cells was, in all cases, found to be reversed upon drug removal.     

Synthesis, characterization, and antitumor activity of rare earth metal complexes of benzoic acid nitrogen mustard

Benzoic acid nitrogen mustard and its rare earth metal complexes were synthesized and characterized by elemental analyses, IR, electronic spectrum, and EPR. The interaction of synthesized complexes with Ct-DNA was investigated and reviewed as a mixed manner of both intercalation and alkylation via fluorescence titration. Their biological activities were also evaluated in K₅₆₂ and Vero cell lines, indicating that complexes had a significant inhibitory effect; however, there was no synergistic effect instead of antagonistic effect compared to benzoic acid nitrogen mustard. The possible mechanism through cellular apoptosis was also explored by comet assay.