Iron dependent degradation of an isothiazolone biocide (5-chloro-2-methyl-4-isothiazolin-3-one)

An isothiazolone biocide, 5-chloro-2-methyl-4-isothiazolin-3-one (CMI), was degraded in the presence of iron. According to the Fe-dependent degradation of CMI, stoichiometric production of chloride was observed. Copper and stainless steel did not enhance the physico-chemical degradation of CMI, whilst phosphate inhibited the Fe-dependent degradation. Neither aerobic nor anaerobic conditions influenced the Fe-dependent CMI degradation. Furthermore, FeO(OH)-powder and Fe(3)O(4)-powder did not lead to the physico-chemical degradation of CMI. Rapid disappearance of CMI was observed in an operating cooling water plant. CMI added to the cooling tower declined from 1.4 mg l(-1) to < 0.1 mg l(-1) in 2 d. This finding is important in optimising the use of CMI and combating resistance if encountered.     

The potentiation of industrial biocide activity with Cu2+. II. Synergistic effects with 5-chloro-2-methyl-4-isothiazolin-3-one

The role of Cu²⁺ in enhancing 5-chloro-2-methyl-4-isothiazolin-3-one (IT) activity was investigated. This study was carried out in two directions. Firstly, the level of enhanced activity from a Cu²⁺ and IT mixture where environmental destruction of IT is minimal was examined. Secondly, the level of protection from Cu²⁺ in environments known to irreversibly reduce IT activity was studied. The bactericidal activities were determined in tryptic soy broth medium, mineral salt base-glucose medium and 0·9 NaCl solution. Under certain conditions, Cu²⁺ also stabilizes and/or protects the sensitive chlorinated IT molecule. Both synergistic activity and stabilization or protection by Cu²⁺ enhance the antimicrobial activity of IT under test conditions. Alternative sequential treatment with IT and Cu²⁺ was used to further characterize enhanced activity. The results suggest synergism. The utility of all the findings was investigated in metalworking fluid.     

Antioxidant activity of 3-methyl-1-phenyl-2-pyrazolin-5-one

Summary

The antioxidant activity of an anti-ischemic agent, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), was examined. The pKa value of MCI-186 is 7.0 and the rate of oxidation of MCI-186 initiated with an azo compound increased with increasing pH, suggesting that the anionic form of MCI-186 is much more reactive than the non-ionic form. The major products were 3-methyl-1-phenyl-2-pyrazolin-4,5-dione (4,5-dione) and 2-oxo-3-(phenylhydrazono)-butanoic acid (OPB). Hydrolysis of 4,5-dione gave OPB. The minor intermediate product was 4-hydroxy-4-(3-methyl-1-phenyl-1H-pyrazolin-5-on-4-yl)-3-methyl-1-phenyl-1H-pyrazolin-5-one (BPOH). The nucleophilic attack of the anionic form of MCI-186 to 4,5-dione is likely to give BPOH. MCI-186 (50 μM) inhibited the aerobic oxidation at 37°C of 5.2 mM unilamellar soybean phosphatidylcholine (PC) liposomal membranes, initiated with a water-soluble initiator, as efficientlyas did ascorbate (100 μM). MCI-186 (50 μM) also inhibited the oxidation of the same PC liposomal membranes, this time initiated with a lipid-soluble initiator, almost as efficiently as did α-tocopherol (2 μM). Furthermore, the combination of MCI-186 with ascorbate or α-tocopherol showed almost complete inhibition of PC oxidation induced by both initiators. These data suggest that MCI-186 may work as a good antioxidant in cellular systems as well as in cell-free systems.     

Synthesis of 2-carboxy-11 beta, 17 beta-dihydroxy-17-methyl-1, 4-androstadien-3-one and related compounds

A series of 2-carboxy-1, 4-androstadien-3-one derivatives and their alkyl esters, were prepared by high-yield syntheses. The compounds were structurally identified by physical methods. All these steroids are characterized by a marked antiglucocorticoid activity that proved long-acting in the case of the ester derivatives. 2-Carboxy-11 beta, 17 beta-dihydroxy-17-methyl-1, 4-androstadien-3-one or roxibolone, and its n-decylester or decylroxibolone, are the most promising derivatives in consideration of their pharmacological properties.     

Control of asymmetric induction in the organometallic synthesis of 3-methyl-(E)-4-hexen-2-one

Bis(μ-methyl-1,3-dimethyl-η³-allylnickel) reacts in the presence of phosphorus(III) ligands (phosphines, phosphites) with CO to give 3-methyl-(E)-4-hexen-2-one. Systematic experiments were performed using chiral ligands containing menthyl or menthoxy groups and different achiral groups on the P atom to determine the influence of ligand structure and concentration on the direction and extent of chiral induction in this ketone synthesis. It could be shown that reversion of enantioselectivity can be obtained not only by the obvious method of reversing the absolute configuration of the ligand (“parity control”) but also by modifying the nonchiral substituents of the phosphorus ligand (“complementarity control”). The synthesis, physical, and spectroscopic properties of several new menthyl phosphines and phosphites are reported.     

Structure-activity relationship of 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone)

This paper describes the discovery of a novel free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone, 1), as a potent antioxidant agent against lipid peroxidation. The structure-activity relationship of edaravone indicated that lipophilic substituents were essential to show its lipid peroxidation-inhibitory activity. In vivo studies revealed that edaravone showed brain-protective activity in a transient ischemia model.     

Production and toxicity of 2,3-dihydro-5-hydroxy-2-methyl-4H-1-benzopyran-4-one by Phialophora gregata

2,3-Dihydro-5-hydroxy-2-methyl-4H-1-benzopyran-4-one, was isolated from 3 week old rice cultures of Phialophora gregata, a soybean pathogen, grown at 25°C. This material in repeated bioassays prevented callus formation on soybean hypocotyl sections at 100 and 200 mg/ml callus culture medium. This is the first report of the production of this metabolite by a member of the Phialphora genus and of its toxicity to soybeans.     

Microbial transformation of 2-amino-4-methyl-3-nitropyridine

Biotransformation of the highly substituted pyridine derivative 2-amino-4-methyl-3-nitropyridine by Cunninghamella elegans ATCC 26269 yielded three products each with a molecular weight of 169?Da which were identified as 2-amino-5-hydroxy-4-methyl-3-nitropyridine, 2-amino-4-hydroxymethyl-3-nitropyridine, and 2-amino-4-methyl-3-nitropyridine-1-oxide. Biotransformation by Streptomyces antibioticus ATCC 14890 gave two different products each with a molecular weight of 169?Da; one was acid labile and converted to the other stable product under acidic conditions. The structure of the stable product was established as 2-amino-4-methyl-3-nitro-6(1H)-pyridinone, and that of the less stable product was assigned as its tautomer 2-amino-6-hydroxy-4-methyl-3-nitropyridine. Four of the five biotransformation products are new compounds. Several strains of Aspergillus also converted the same substrate to the lactam 2-amino-4-methyl-3-nitro-6(1H)-pyridinone. Microbial hydroxylation by C. elegans was found to be inhibited by sulfate ion. In order to improve the yield and productivity of the 5-hydroxylation reaction by C. elegans, critical process parameters were determined and Design of Experiments (DOE) analyses were performed. Biotransformation by C. elegans was scaled up to 15-l fermentors providing 2-amino-5-hydroxy-4-methyl-3-nitropyridine at ca. 13?% yield in multi-gram levels. A simple isolation process not requiring chromatography was developed to provide purified 2-amino-5-hydroxy-4-methyl-3-nitropyridine of excellent quality.     

Synthesis and in vitro evaluation of N-alkyl-3-hydroxy-3-(2-imino-3-methyl-5-oxoimidazolidin-4-yl)indolin-2-one analogs as potential anticancer agents

A series of novel 3-hydroxy-3-(2-imino-3-methyl-5-oxoimidazolidin-4-yl)indolin-2-one analogs (3) have been synthesized under microwave irradiation and conventional heating methods. These analogs were evaluated for in vitro cytotoxicity against a panel of 57 human tumor cell lines. Compound 3o had GI₅₀ values of 190 nM and 750 nM against A549/ATTC non-small cell lung cancer and LOX IMVI melanoma cell lines, respectively, and both 3n and 3o exhibited GI₅₀ values ranging from 2 to 5 μM against CCRF-CEM, HL-60(TB), K-562, MOLT-4, and RPMI-8226 leukemia cell lines. These results indicate that N-4-methoxybenzyl-3-hydroxy-(2-imino-3-methyl-5-oxo-4-yl)indolin-2-one analogs may be useful leads for anticancer drug development.     

Metabolism of 17β-hydroxy-2α-methyl-5α-androstan-3-one in the rabbit

The neutral urinary excretion products of 17β-hydroxy-2α-methyl-5α-androstan-3-one from the rabbit dosed orally were investigated. Together with oxidation-reduction of the oxygen functions at C-3 and C-17 hydroxylation occurred at C-15, C-16, and at the 2α-methyl positions of the steroid nucleus.     

Synthesis,spectral and antimicrobial evaluation of some novel 1-methyl-3-alkyl-2,6-diphenylpiperidin-4-one oxime carbonates

Synthesis of some novel biologically active piperidin-4-one oxime carbonates from 1-methyl-3alkyl-2,6-diphenylpiperidin-4-one oximes and substituted chloroformates was carried out in the presence of potassium carbonate as base and tetrabutylammonium bromide (TBAB) as catalyst. The newly synthesized compounds were characterized by IR, ¹H, ¹³C NMR and LC–mass spectra. Based on the ¹H NMR analysis, all the compounds were found to adopt normal chair conformation with equatorial orientation of all the substituents. For all the synthesized compounds (5a–5l) antimicrobial activity has been tested against bacterial and fungal strains using Streptomycin and Amphotericin B as standards.     

Atropisomeric quinazolin-4-one derivatives are potent noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists

Piriqualone (1) was found to be an antagonist of AMPA receptors. Structure activity optimization was conducted on each of the three rings in 1 to afford a series of potent and selective antagonists. The sterically crowded environment surrounding the N-3 aryl group provided sufficient thermal stability for atropisomers to be isolated. Separation of these atropisomers resulted in the identification of (+)-38 (CP-465,022), a compound that binds to the AMPA receptor with high affinity (IC50 = 36 nM) and displays potent anticonvulsant activity.     

Identification of 3-hydroxy-6-methyl-2H-pyran-2-one from pyrolysis of phosphoric acid-treated cellulosic materials

The hydrogen isotope-effect that occurs in vitro during myo-inositol 1-phosphate synthase-catalyzed conversion of d-[5-³H]glucose 6-phosphate into myo-[2-³H]inositol 1-phosphate has been used to compare the functional role of the nucleotide sugar oxidation-pathway with that of the myo-inositol oxidation-pathway in germinating lily pollen. Results reveal a significant difference between the ³H/¹⁴C ratios of glucosyl and galactosyluronic residues from pectinase-amyloglucosidase hydrolyzates of the 70 % ethanol-insoluble fraction of d-[5-³H, 1-¹⁴-C]glucose-labeled, germinating lily pollen. This isotope effect at C-5 of d-glucose that occurred during its conversion into d-galactosyluronic residues of pectic substance is not explained by loss of ³H when UDP-d-[5-³H, 1-¹⁴C]glucose is oxidized by UDP-d-glucose dehydrogenase from germinating lily pollen. The evidence obtained from this study favors a functional role for the myo-inositol oxidation pathway during in vivo conversion of glucose into galactosyluronic residues of pectin in germinating lily pollen.     

Antimicrobial activity of 3-methyl-5-furfurylidene-2-thioxo-4-thiazolidones

Substituted 3-methyl-5-furfurylidene-2-thioxo-4-thiazolidones1 –17 were tested for their action againstBacillus pumilus, B. brevis andB. megaterium and againstAspergillus flavus, A. fumigatus andA. niger. Most of the compounds possessed an activity against both bacteria and fungi. These compounds were also tested for their effectiveness as virus inhibitors employingNicotiana glutinosa as assay host against tobacco mosaic virus. Most of them exhibited potential antiviral activity bothin vitro andin vivo.     

Synthesis and antiviral evaluation of 3-hydroxy-2-methylpyridin-4-one dideoxynucleoside derivatives

We describe the synthesis and the antiviral evaluation of novel and β dideoxynucleoside derivatives in which the base has been replaced by a 3-hydroxy-2-methylpyridin-4-one. The syntheses were successfully achieved by the use of the standard Vorbrüggen coupling conditions. Moderate activity of these compounds were found on herpes simplex virus (HSV) type 1 and type 2.     

Synthesis and study of anti-HIV-1 RT activity of 5-benzoyl-4-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one derivatives

In the present study, a series of fourteen 5-benzoyl-4-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one derivatives were designed, synthesized and characterized by appropriate spectral analysis. Further, titled compounds were in-vitro screened against wild HIV-1 RT enzyme using ELISA based colorimetric assay, in which four compounds significantly inhibited the RT activity with IC₅₀ ≤ 25 µM. Moreover, two significantly active compounds of the series, A10 and A11 exhibited IC₅₀ values 8.62 and 6.87 µM respectively, during the in-vitro assay. Structure Activity Relationship (SAR) studies were performed for the synthesized compounds in order to estimate the effect of substitution pattern on the RT inhibitory potency. The cytotoxicity of the synthesized compounds was evaluated against T lymphocytes. Further, putative binding modes of the significantly active (A11) and the least active (A4) compounds with wild HIV-1 RT were also investigated using docking studies.     

The identification of 17 -hydroxy-17-methyl-1,4-androstadien-3-one as a metabolite of the anabolic steroid drug 17 -hydroxy-17-methyl-1,4-androstadien-3-one in man

The more polar of the two major urinary metabolites of methandrostenolone, 17β-hydroxy-17-methyl-1,4-androstadien-3-one, in man has already been identified as 6β-hydroxymethandrostenolone, 6β, 17β-dihydroxy-17-methyl-1,4-androstadien-3-one. The other metabolite has now been identified as the 17-epimer of methandrostenolone, 17α-hydroxy-17-methyl-1,4-androstadien-3-one. The compound was isolated from the freely extractable neutral fraction of urine following the administration of 5 mg of the drug to normal men. The relevant chromatographic fractions from thin layer and gas liquid systems were identified by carbon skeleton chromatography. The 17-epimer has been synthesised, details of which are included, and the previously unidentified metabolite was found to be identical with the synthetic compound.     

Synthesis of the allylic gonadal steroids, 3 alpha-hydroxy-4-pregnen-20-one and 3 alpha-hydroxy-4-androsten-17-one, and of 3 alpha-hydroxy-5 alpha-pregnan-20-one

A method for the convenient synthesis of the recently isolated allylic gonadal steroids, 3 alpha-hydroxy-4-pregnen-20-one (3 alpha-dihydroprogesterone; 3 alpha-DHP) and 3 alpha-hydroxy-4-androsten-17-one (3 alpha-HA), was developed using 4-pregnene-3,20-dione (progesterone) and 4-androstene-3,17-dione as substrates and potassium trisiamylborohydride (KS-Selectride) as reducing agent. Similar reactions were also used for the reduction of 5 alpha-pregnane-3,20-dione to 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha-HP). The yields were about 15%, 50%, and greater than 90% for 3 alpha-DHP, 3 alpha-HA and 3 alpha-HP, respectively. Structures of the products, including the 3 beta-isomers and the 17 alpha-epimer, formed in these reactions were determined by NMR and mass spectroscopic methods.