Synthesis and structure of new tetracopper(II) complexes with N-benzoate-N'-[3-(diethylamino)propyl]oxamide as a bridging ligand: The influence of hydrophobicity on enhanced DNA/BSA-binding and anticancer activity.

Two new tetracopper(II) complexes bridged by N-benzoate-N'-[3-(diethylamino)propyl]oxamide (H3bdpox), and ended with 4,4'-dimethyl-2,2'-bipyridine (Me2bpy) or 2,2'-bipyridine (bpy), namely [Cu4(bdpox)2(Me2bpy)2](pic)2 (1) and [Cu4(bdpox)2(bpy)2](pic)2·2H2O (2) (where pic denotes the picrate anion) have been synthesized and characterized by X-ray single-crystal diffraction and other methods. In both complexes, four copper(II) ions are bridged alternately by the cis-oxamido and the carboxylato groups of two bdpox(3-) ligands to form a centrosymmetric cyclic tetranuclear cation, in which, the copper(II) ions at the endo- and exo-sites of cis-bdpox(3-) ligand have square-planar and square-pyramidal coordination geometries, respectively. The reactivity towards DNA/BSA suggests that these complexes can interact with HS-DNA through the intercalation mode and the binding affinity varies as 1>2 depending on the hydrophobicity, and effectively quench the fluorescence of protein BSA via a static mechanism. In vitro anticancer activities showed that the two complexes are active against the selected tumor cell lines, and the anticancer activities are consistent with their DNA-binding affinity.

Discovery of tumor-specific irreversible inhibitors of stearoyl CoA desaturase.

A hallmark of targeted cancer therapies is selective toxicity among cancer cell lines. We evaluated results from a viability screen of over 200,000 small molecules to identify two chemical series, oxalamides and benzothiazoles, that were selectively toxic at low nanomolar concentrations to the same 4 of 12 human lung cancer cell lines. Sensitive cell lines expressed cytochrome P450 (CYP) 4F11, which metabolized the compounds into irreversible inhibitors of stearoyl CoA desaturase (SCD). SCD is recognized as a promising biological target in cancer and metabolic disease. However, SCD is essential to sebocytes, and accordingly SCD inhibitors cause skin toxicity. Mouse sebocytes did not activate the benzothiazoles or oxalamides into SCD inhibitors, providing a therapeutic window for inhibiting SCD in vivo. We thus offer a strategy to target SCD in cancer by taking advantage of high CYP expression in a subset of tumors.

Effect of oxamic analogues on functional mice sperm parameters.

The present study evaluates the effect of oxamate derivatives (N-ethyl, N-propyl, N-butyl oxamates) on functional murine sperm parameters, towards a new male non-hormonal contraceptive. These derivatives are selective inhibitors of lactate dehydrogenase-C4 (LDH-C4). LDH-C4 is a sperm-specific enzyme that plays an important role in ATP production for maintaining progressive motility as well as to induce capacitation and hyperactivation. The results demonstrate that all oxamate derivatives selectively inhibited LDH-C4 in mouse sperm extracts. The IC(50) values for hexokinase and glyceraldehyde-3-phosphate dehydrogenase were at least an order of magnitude greater than LDH-C4 IC(50) values. Prodrugs of oxamate derivatives assayed on sperm cells diminished normal sperm motility parameters, acrosome reaction, and cell viability in a concentration dependent manner. Also, we performed in vivo studies to determine the potential toxicity and possible contraceptive ability of these inhibitors. Mouse sperm were more sensitive to the N-butyl oxamate ethyl ester (NBOXet). Furthermore, results showed that NBOXet was of a low toxicity substance that diminished the total and progressive motility as well as the kinematic parameters of sperm cells. Data from in vitro and in vivo studies showed that N-butyl oxamate and its prodrug, are selective inhibitors of sperm LDH-C4, has low toxicity, and inhibits sperm progressive motility, offering some of the desirable characteristics of a male contraceptive: effect, low toxicity, and selectivity.

Design and synthesis of novel diphenyl oxalamide and diphenyl acetamide derivatives as anticonvulsants.

A series of novel N(1) -substituted-N(2) ,N(2) -diphenyl oxalamides 3a-l were synthesized in good yield by stirring diphenylcarbamoyl formyl chloride (2) and various substituted aliphatic, alicyclic, aromatic, heterocyclic amines in DMF and K(2) CO(3) . Also 2-substituted amino-N,N-diphenylacetamides 5a-m were designed by pharmacophore generation and synthesized by stirring 2-chloro-N,N-diphenylacetamide (4) and various substituted amines in acetone using triethyl amine as a catalyst. All the synthesized compounds were screened for anticonvulsant activity in Swiss albino mice by MES and ScPTZ induced seizure tests. Neurotoxicity screening and behavioral testing was also carried out. Some of the synthesized test compounds were found to be more potent than the standard drug.

Identification of bis(agmatine)oxalamide in venom from the primitive hunting spider, Plectreurys tristis (Simon).

N, N'-bis(4-guanidinobutyl)oxalamide, a novel bis(agmatine)oxalamide, is identified as a major component (8 micrograms/microliters) and the predominant acylpolyamine in venom from the primitive hunting spider, Plectreurys tristis. The function of this compound is unknown since it does not confer insecticidal or fungicidal activity in the systems examined.

Estudio de algunos factores que influyen en la concentración de ácido orálico en equisetum bogotense KBH "cola de caballo" zea mays L. "maiz". Solanum tuberosum L. "papa" y su cuantificación por lo métodos de titulación permanganometrica y de absorción atómica / Some factors study of Oralic acid in equisetum bogotense KBH \"cola de caballo\", zea mays L. \"maiz\" Solanum tuberosum L. \"papa\" y su cuantification by the methods of permanganometric titulation by atomic absortion

Se usaron 3 plantas diuréticas. Determinar ácido oxálico en las diferentes drogas tanto crudas como cocidas en forma individual y combinado, usando los métodos de la ADAC. La edad de la planta, es determinante en el contenido de ácido oxálico. Las muestras crudas lanzaron mayor porcentaje de ácido oxálico. Se comprobó que existen algunos factores determinantes que influyen directa o indirectamente en la concentración de ácido oxálico en los vegetales.

Urothelial lesions in mice given 4-ethylsulfonylnaphthalene-1-sulfonamide, acetazolamide, and oxamide.

4-Ethylsulfonylnaphthalene-1-sulfonamide, acetazolamide and oxamide were administered in the diet to female BALB/c mice for varying periods of time from three to eighty weeks. All three compounds induced lesions in the urothelium. In the bladder, these included simple hyperplasia, nodular hyperplasia, inflammation and calculi. Similar lesions were observed in the ureter and urethra, along with a novel lesion, diverticulum, in the ureter. The diverticular lesions existed as down-growths of the transitional epithelium which often extended from the mucosa through the muscle layers to the adventitial surface. The etiology of the lesions appeared to be related to urinary physiological alterations (crystalluria, calculi, hypoosmolality) caused by administration of the compounds.

The role of urinary physiological changes in the genesis of urothelial lesions in mice given 4-ethylsulfonylnaphthalene-1-sulfonamide, acetazolamide, and oxamide.

BALB/c female mice were administered several compounds, including 4-ethylsulfonylnaphthalene-1-sulfonamide, acetazolamide, and oxamide, in the diet for six weeks. Fresh urine samples were analyzed three times per week for pH, osmolality, micro-crystals, and protein; and a histopathological evaluation was made of the urothelium at the end of the six weeks test. Incidences of hyperplasia, nodular hyperplasia, vacuolization, ulceration and acute inflammation of the bladder urothelium appeared to be related to the osmolality of the urine and the micro-crystalluria experienced by the mice. Correlation coefficients between lesions and urinary osmolality or crystals were -0.69 (p less than 0.0001) and 0.31 (p less than 0.03), respectively, at the 5% significance level.

Synthesis and anti-inflammatory activity of certain new N,N'-oxamides.

Some new amides of substituted oxamic acid which embody different moieties of the anti-inflammatory drugs were prepared through two routes of synthesis. The physico-chemical properties as well as the anti-inflammatory activity of these compounds were determined. Preliminary pharmacological testing revealed the superiority of most of the screened compounds as anti-inflammatory agents with relatively low toxicity as compared with acetylsalicylic acid. Correlation between structure and biological activity was suggested.

The influence of polyglycolic acid (Dexon) on the formation of urinary calculi in rats fed with oxamide.

Rats fed with 2% oxamide diet were considered as a model for the patient with a tendency to stone formation. Polyglycolic acid (Dexon) sary stream caused formation of oxamide deposits in a percentage as high as that observed with silk sutures. A high degree of toxicity was observed with the chosen concentration of oxamide diet (weight loss, mortality). The importance of oxamide concentration is underlined for further experiments on the influence of suture material on urinary infection and stone formation.