2801-04-9

Sodium bisdithiocarbamate is used to form neutral metal complexes with metals of the hydrogen sulfide group.The hydroxy groups present in NaHEDC cause the metal complexes to be water-soluble at low concentrations.The complexed metal ions can be separated into groups or concentrated from very dilute solution by sorption on a small column of XAD-4 resin.Selectivity is achieved by pH adjustment or by masking agents.The sorbed metal complexes are eluted with acidic ethanol for subsequent measurement by AAS or absorption spectrophotometry.Applications to show the utillity of the method include concentration of tracemetals from uranium.

The worldwide prevalence of NDM-1-producing Gram-negative pathogens has drastically undermined the clinical efficacy of carbapenems, prompting a need to devise an effective strategy to preserve their clinical value. Here we constructed a focused compound library of dithiocarbamates and systematically evaluated their potential synergistic antibacterial activities combined with copper. SA09-Cu exhibited excellent inhibition against a series of clinical NDM-1-producing carbapenem-resistant Enterobacteriaceae (CRE) in restoring meropenem effect, and slowed down the development of carbapenem resistance. Enzymatic kinetic and isothermal titration calorimetry studies demonstrated that SA09-Cu was a noncompetitive NDM-1 inhibitor. The electron paramagnetic resonance (EPR) and X-ray photoelectron spectroscopy (XPS) revealed a novel inhibition mechanism, which is that SA09-Cu could convert NDM-1 into an inactive state by oxidizing the Zn(II)-thiolate site of the enzyme. Importantly, SA09-Cu showed a unique redox tuning ability, and avoided to be reduced by intracellular thiols of bacteria. In vivo experiments indicated that SA09 combined with CuGlu could effectively potentiate MER's effect against NDM-1-producing E. coli (EC23) in the murine infection model. This study provides a highly promising scaffold in developing novel inhibitors to combat NDM-1-producing CREs.

A series of H2S–CO dual-donors [Mn(CO)4CS2NR1R2] was synthesized, and evaluated from toxicity and bioactivity. The CO–H2S measuring test showed all the complexes not only released CO, but released H2S. The resulting data of cytotoxicity showed all the complexes had activities against the cell proliferation; among them, complexes 1, 2 and 7 displayed higher activities than the others, and their potencies were close to cis-platinum (DDP); whereas the precursors A1-A22 had almost no activities against all five tumor cell lines and W138 cell line proliferation. It is worth noting that complex 1 displayed the highest activity to MCF-7, complex 2 displayed the highest activity to HePG2, and complex 7 showed selectivity inhibition to both A549 and HeLa. The developmental toxicities of the complex were assessed using zebrafish embryos. The results showed complexes 1 and 2 had effect on the mortality and hatching rate of zebrafish embryos in dose-dependent manner. They caused zebrafish malformations when they were over 10 μM. Meanwhile, they displayed dose-dependent toxicities to larval zebrafish. In the test of bio-activities, complexes 1 and 2 had strong anti-inflammatory activities; they not only down-regulated the expression levels of iNOS and TNF-α up-regulated the expression of HO-1 and IL-10, but also up-regulated COX-2 levels. In contrast, the precursor compound (A1 or A2) displayed lower anti-inflammatory activity than the corresponding complex, which suggests both the CO and H2S from the complex took synergistic effects in the process of anti-inflammation. In addition, the complex showed antihypertensive effect and myocardial protection. This effect also possibly resulted from this synergistic effect. All these suggest the complexes have potential to be candidate medicines.

A carbonic anhydrase inhibitor which comprises a compound of general formula: R 1RZN-CSz-M+ for use in the treatment of microbial infection, eye disease or cancer; wherein R1 and R2 are each independently selected from H or an organic substituent, or together form a ring, and optionally contain one or more heteroatoms; wherein R and R2 together comprise at least 5 carbon atoms or at least 2 carbon atoms and a heteroatom, or R2 comprises at least 4 carbon atoms; and wherein M+ comprises a monovalent cation

A series of dithiocarbamates were prepared by reaction of primary/secondary amines with carbon disulfide in the presence of bases. These compounds were tested for the inhibition of four human (h) isoforms of the zinc enzyme carbonic anhydrase, CA (EC 4.2.1.1), hCA I, II, IX, and XII, involved in pathologies such as glaucoma (CA II and XII) or cancer (CA IX). Several low nanomolar inhibitors targeting these CAs were detected. The X-ray crystal structure of the hCA II adduct with morpholine dithiocarbamate evidenced the inhibition mechanism of these compounds, which coordinate to the metal ion through a sulfur atom from the dithiocarbamate zinc-binding function. Some dithiocarbamates showed an effective intraocular pressure lowering activity in an animal model of glucoma.

Compounds, pharmaceutical compositions and methods for the therapeutic delivery of carbon monoxide to humans and other mammals that employ Mn complexes having CO ligands, and additional halogen, monodentate and/or bidentate ligands, wherein the additional ligands do not occupy trans positions relative to each other.

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