Syntheses and antimicrobial activities of some 4-aza-sitostane derivatives

Research into the chemical and pharmacological properties of aza­steroids has become of interest because of their potential value as pharmacodynamic and chemotherapeutic agents. A nitrogen atom, for example, would be able to interact, unlike carbon, with a variety of sites in enzymes by means of ionic-ionic, ionic-dipole, dipole-dipole and hydrogen.bonds. Azasteroids having a nitrogen, atom might be adsorbed more strongly or in a different orientation to a given enzyme, and also may produce.a different biologic effect with a new spectrum of biological activities. The pharmacological.activities of a number of synthetic azasteroids, have been reported. This investigation is concerned with the synthesis of some aza-sitostanes, a study of their antimicrobial properties, and the synthesis of sufficient quantities for screening for hypocholesterolemic and insect chemosterilant properties

Diazo Compounds and Phenyliodonium Ylides in Inter- and Intramolecular Cyclopropanations Catalyzed by Dirhodium(II). Synthesis and Chiral Resolution by GC versus HPLC

Summary.: The dirhodium(II)-catalyzed intermolecular cyclopropanation of a set of olefins with either diazo free phenyliodonium ylides or diazo compounds afforded cyclopropanes derived from Meldrum's acid, dimethyl malonate, (silanoxyvinyl)diazoacetates, 3,3,3-trifluoro-2-diazopropionate, ethyl diazo(triethyl)- and (dimethylphenyl)silylacetate with moderate to high yield in either racemic or enantio-enriched forms. The intramolecular cyclopropanation of triethylsilyl-substituted allyl diazoacetates in the presence of the chiral rhodium(II) catalyst [Rh2(s-nttl)4] in toluene afforded the corresponding cyclopropanes with up to 37% ee. An efficient chiral separation method based on enantioselective GC and HPLC was developed. The method provides information about the chemical yields of the cyclopropane products, enantioselectivity, substrate specifity, and catalytic activity of the chiral catalysts used in the inter- and intramolecular cyclopropanation reactions and avoids time-consuming work-up procedure

Supramolecular Dynamics of Thalidomide and its Derivatives in Water-Sediment System

The contamination of drug residues, including chiral ones, is not acceptable in earth’s ecosystem. The dynamicity of enantiomers of thalidomide and its derivatives (3-methyl thalidomide, 3-ethyl thalidomide, and 3-butyl thalidomide) was ascertained at supramolecular level in water-sediment system using solid phase extraction (SPE) and stereoselective HPLC. Enantiomeric separation of these drugs was carried out on Ceramosphere RU-2 (25 cm 3 0.46 cm, particle size 50 lm) chiral column using pure ethanol (1.0 ml/min) as eluent at 230 nm detection. Retention times, capacity, separation, and resolution factors of the enantiomers of these drugs were in the range of 20.0–36.0, 2.08–3.93, 1.35–1.57, and 1.0–2.0 min, respectively. Percentage recoveries of the enantiomers in SPE were in the range of 90.0 to 95.0 in water-sediment system. Langmuir and Freundlich model were best fitted for dynamic equilibrium concentrations at different experimental parameters. Thalidomide and its derivatives follow first-order kinetics at dynamic equilibrium. The rate constants of chiral interconversions were 0.390 and 0.385 days21 for S- and R-enantiomers, respectively. The uptake of thalidomide by sediment is quite good and of endothermic nature indicating good self-purifi-cation capacity of the nature for such toxic species. Chirality 00:000–000, 2009. VVC 2009 Wiley-Liss, Inc

Supramolecular Dynamics of Thalidomide and its Derivatives in Water-Sediment System

The contamination of drug residues, including chiral ones, is not acceptable in earth’s ecosystem. The dynamicity of enantiomers of thalidomide and its derivatives (3-methyl thalidomide, 3-ethyl thalidomide, and 3-butyl thalidomide) was ascertained at supramolecular level in water-sediment system using solid phase extraction (SPE) and stereoselective HPLC. Enantiomeric separation of these drugs was carried out on Ceramosphere RU-2 (25 cm 3 0.46 cm, particle size 50 lm) chiral column using pure ethanol (1.0 ml/min) as eluent at 230 nm detection. Retention times, capacity, separation, and resolution factors of the enantiomers of these drugs were in the range of 20.0–36.0, 2.08–3.93, 1.35–1.57, and 1.0–2.0 min, respectively. Percentage recoveries of the enantiomers in SPE were in the range of 90.0 to 95.0 in water-sediment system. Langmuir and Freundlich model were best fitted for dynamic equilibrium concentrations at different experimental parameters. Thalidomide and its derivatives follow first-order kinetics at dynamic equilibrium. The rate constants of chiral interconversions were 0.390 and 0.385 days21 for S- and R-enantiomers, respectively. The uptake of thalidomide by sediment is quite good and of endothermic nature indicating good self-purifi-cation capacity of the nature for such toxic species. Chirality 00:000–000, 2009. VVC 2009 Wiley-Liss, Inc

Chiral Separation of Econazole by High Performance Liquid Chromatography Method using Cyclodextrin as Chiral Column

The chiral separation of econazole, an antifungal drug with one chiral center has been successfully carried out using the high-performance liquid chromatography (HPLC) method. Enantioresolution of econazole (Rs = 2.29) was achieved using cyclodextrin-based chiral column (Astec Cyclobond, 25 cm × 4.6 mm × 5 μm), mobile phase composition of acetonitrile : water (0.2% HCOOH) (20:80, v/v), and UV detection of 220 nm.The optimized HPLC method has been applied for the quantitative determination of econazole in the pharmaceutical (liquid) sample withpercentage recovery of 100.75 % (RSD =   0,95%; n = 3). The effect of several HPLC parameters on the chiral separation of econazole was also evaluated and the method was successfully validated in terms of linearity, accuracy, precision, and selectivity. The present HPLC method was simple, short analysis time, and high resolution

Inhibition of growth of Leishmania donovani promastigotes by newly synthesized 1,3,4-thiadiazole analogs

AbstractLeishmania donovani, the causative agent of visceral leishmaniasis, is transmitted by sand flies and replicates intracellularly in their mammalian host cells. The emergence of drug-resistant strains has hampered efforts to control the spread of the disease worldwide. Forty-four 1,3,4-thiadiazole derivatives and related compounds were tested in vitro for possible anti-leishmanial activity against the promastigotes of L. donovani. Micromolar concentrations of these agents were used to study the inhibition of multiplication of L. donovani promastigotes. Seven compounds were identified with potential antigrowth agents of the parasite. Compound 4a was the most active at 50μM followed by compound 3a. These compounds could prove useful as a future alternative for the control of visceral leishmaniasis

Stereoselective HPLC assay of donepezil enantiomers with UV detection and its application to pharmacokinetics in rats

Abstract This investigation describes a new precise, sensitive and accurate stereoselective HPLC method for the simultaneous determination of donepezil enantiomers in tablets and plasma with enough sensitivity to follow its pharmacokinetics in rats up to 12 h after single oral dosing. Enantiomeric resolution was achieved on a cellulose tris (3,5-dimethylphenyl carbamate) column known as Chiralcel OD, with UV detection at 268 nm, and the mobile phase consisted of n-hexane, isopropanol and triethylamine (87:12.9:0.1). Using the chromatographic conditions described, donepezil enantiomers were well resolved with mean retention times of 12.8 and 16.3 min, respectively. Linear response (r > 0.994) was observed over the range of 0.05-2 g/ml of donepezil enantiomers, with detection limit of 20 ng/ml. The mean relative standard deviation (R.S.D.%) of the results of within-day precision and accuracy of the drug were ≤10%. There was no significant difference (p > 0.05) between inter-and intra-day studies for each enantiomers which confirmed the reproducibility of the assay method. The mean extraction efficiency was 92.6-93.2% of the enantiomers. The proposed method was found to be suitable and accurate for the quantitative determination of donepezil enantiomers in tablets. The assay method also shows good specificity to donepezil enantiomers, and it could be successfully applied to its pharmacokinetic studies and to therapeutic drug monitoring

Ultrasonic-assisted extraction of curcumin complexed with methyl-beta-cyclodextrin

Turmeric flavour is important in Asian cuisine; however, the production of turmeric-based ingredient with the current method of extraction of turmeric oleoresin is very laborious, time consuming and consumes large amount of solvent, coupled with limited solubility in aqueous solution, which limits its application to food system. The extract was optimised by determining the content of three marker curcuminoid compounds, namely, curcumin (C), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC). The optimised extraction parameters for ultrasonic-assisted extraction (UAE) with aqueous extraction solvent for curcuminoids were amplitude of 100, particle size of 0.30–0.60 mm, extraction time of 20 min, extraction solvent volume of 10 mL and extraction temperature of 60 °C. The applications showed remarkable improvements in terms of reduced extraction time, solvent consumption, extraction yield and the quality of extracts. The turmeric oleoresin was successfully solubilised in aqueous solution by forming inclusion complex with methyl-ß-cyclodextrin (Mß-CD). Phase solubility studies used curcumin as a marker compounds to represent turmeric oleoresin. In the presence of Mß-CD, the curcumin was enhanced. Result from characterisation of inclusion complexes with Fourier transform infrared (FTIR) spectrometry indicates that all the mixing methods were found to be suitable for encapsulation. However, scanning electron microscopy (SEM) shows a drastic change in particle sizes, indicating a formation of a new solid phase in kneading method, implying it as the best mixing method

Chiral Alkaloid Analysis

Alkaloids are distributed in plant kingdom and play important role in protection, germination as well as plant growth stimulants. Most of them are chiral compounds and are clinically administered as the racemic mixture, even though its enantiomers have been known to exert different pharmacological activity. Liquid chromatography using chiral stationary phases (CSP) proved to be an essential tool with a wide range of applications, including analysis of the stereochemistry of natural compounds. This review gives an overview of chiral separation alkaloids that were used in theoretical studies and/or applications in recent years. It shows the possibilities of polysaccharide CSPs have now also been established as the first-choice of chiral phases for enantiomer separation

Simple adsorption of Candida rugosa lipase onto multi-walled carbon nanotubes for sustainable production of the flavor ester geranyl propionate

In this study, geranyl propionate was enzymatically synthesized from geraniol and propionic acid using Candida rugosa lipase immobilized on acid functionalized multi-walled carbon nanotubes. The efficiency of the CRL-MWCNTs biocatalysts to catalyze the esterification production of geranyl propionate (solvent log P, alcohol:acid molar ratio and thermal stability) was compared with the free CRL for parameters. The use of CRL-MWCNTs in n-heptane (log P 4.0) and alcohol:acid molar ratio of 5:1 resulted in a 2-fold increased conversion frequency as compared to the free CRL for the production of geranyl propionate, in addition to a noteworthy 2-fold enhanced thermal stability