New type of amide conjugates of steroid and bile acids with D-glucosamine 1 and 2 were prepared. Title compounds are prepared via acid chloride or using N-[({[(1E)-1-cyano-2-ethoxy-2-oxoethylidene]amino}oxy)(dimethylamino)methylidene]-N-methylmethanaminium tetrafluoroborate as condensation agent. They were examined for gelation properties with negative results. Per-O-acetylated D-glucosamine hydrochloride was prepared in one step procedure from D-glucosamine hydrochloride by acetylation in a mixture of acetyl chloride and acetic acid.
H-point standard addition method(HPSAM) with simultaneous addition of both analytes in nonaqueous solution was applied for determination of Atorvastatin (AT) and Amlodipine (AML). The results showed that simultaneous determination could be performed with the ratio 0.16 to 4.3 of AT–AML. The corresponding values of LOD were obtained for AT and AML 1.2 × 10–6 and 9 × 10–7 mol l–1, respectively, and the corresponding values of LOQ were obtained for AT and AML 4 × 10–6 and 3 × 10–6 mol l–1, respectively. Underworking conditions, the proposed method was successfully applied for simultaneous determination of AT and AML in several synthetic mixtures and Amostatine tablets.
We describe a relatively simple method for the determination of glutathione (GSH) and glutathione disulfide (GSSG) in human whole blood. We have used an HPLC with coulometric electrochemical detection for the simultaneous measurement of GSH and GSSG. Diluted and filtered trichloroacetic acid extracts were injected directly into the HPLC system and were eluted isocratically on a Polaris 5u C18-A, 250 × 4.6 mm analytical column. Glutathione in samples extracted with trichloroacetic acid and diluted with 1.0 mM hydrochloric acid was stable at 4 °C for at least 8 h. The analytical performance of this method is satisfactory: the intra-assay and inter-assay coefficients of variation were below 10%. Quantitative recoveries from spiked whole blood samples were at intervals 91.6–97.6% for GSH and 85.0–104.4% for GSSG. The linear range is 5.0–2000.0 µmol/l, with a detection limit of 2.1 µmol/l (signal-to-noise ratio = 3) for GSH and 2.0–250.0 µmol/l, with a detection limit of 0.9 µmol/l for GSSG.
The cyclic voltammetric behavior of minoxidil was studied in a buffer with pH 3. Contradictory to that mentioned in a previously published work, the cyclic voltammogram of minoxidil exhibited a single 2-electron irreversible reduction wave in a buffer with pH 3. This wave was attributed to the reduction of the N›O bond. The cathodic differential pulse wave height decreased on the increase of pH till it disappeared in solution with pH 7.2. The quantitative trace determination of minoxidil was studied at a hanging mercury drop electrode by adsorptive cathodic stripping voltammetry. A fully validated sensitive procedure based on controlled adsorptive accumulation of the drug onto a HMDE was developed for its direct determination. Accumulation of minoxidil was found to be optimized in 0.1 M Britton–Robinson buffer with pH 2.0 as supporting electrolyte under the following conditions: accumulation potential –0.2 V, accumulation time 40 s, scan rate 40 mV s–1 and pulse height 50 mV. The proposed procedure was applied successfully for determination of minoxidil in its topical solution and illegal shampoo and cream. The mean recoveries of the minoxidil were 99.8, 97.8 and 96.7% and with RSD of 0.86, 1.24 and 1.89% in pharmaceutical topical solution, shampoo and cream, respectively.
A new, rapid and very sensitive electrochemical method for the determination of a new pesticide clothianidin in tap and river water was developed. The electrochemical reduction and determination of clothianidin have been carried out at a hanging mercury drop electrode (HMDE) in various aqueous solutions in the pH range of 2–10 by cyclic voltammetry (CV) and cathodic stripping square wave voltammetry (SW CSV). The best results were obtained for the clothianidin determination by SW CSV method in 0.04 mol l–1 Britton Robinson buffer at pH 8.1. Various conditions of the procedure were checked. Elaborated electroanalytical procedure enable clothianidin determination in the concentration range of 2.0 × 10–8–9.9 × 10–7 mol l–1. The limit of detection (LOD) and limit of quantification (LOQ) were obtained as 2.00 × 10–9 and 2.36 × 10–8 mol l–1, respectively. Precision and accuracy of the developed method were checked by recovery studies in spiked tap and river water. The voltammetric determination has been validated using HPLC with UV detection.
A simple, rapid, reliable and fully validated differential pulse adsorptive cathodic stripping voltammetric procedure has been developed for determination of the curcumin in human serum and turmeric, based on its electrochemical reduction at a hanging mercury drop electrode. The Britton–Robinson (BR) buffer of pH 9.5 was found to be reasonable as a supporting electrolyte for the assay of the compound. The effect of different parameters, such as pH, accumulation potential and accumulation time, on the sensitivity of method was evaluated. Under the optimized conditions (accumulation potential –0.3 V, accumulation time 50 s, BR buffer pH 9.5), curcumin was generated one irreversible cathodic peak. This cathodic peak showed a linear dependence on the concentration of curcumin over the range of 5.0 × 10–9–2.8 × 10–7 mol l–1. The obtained detection limit under the optimal experimental conditions is 1.5 × 10–9 mol l–1 after 50 s of the accumulation time. The relative standard deviation of 1.12% for concentration of 5.0 × 10–8 mol l–1 with 50 s accumulation time was obtained. The procedure was used successfully to the assay of the curcumin in turmeric and spiked human serum, and a good agreement was obtained between the results of the proposed method and high performance liquid chromatography (HPLC) analysis.
On-the-fly surface hopping nonadiabatic photodynamical simulations using hybrid quantum mechanical/molecular mechanical approach of 4-aminopyrimidine were performed to model the relaxation mechanism of adenine within DNA double strand. The surrounding bases do not affect the overall ring-puckering relaxation mechanisms significantly, however, interesting hydrogen-bond dynamics is observed. First, formation of intra-strand hydrogen bonds is found. It is shown that this effect speeds up the decay process. In addition, the Watson–Crick structure is altered by breaking one of the inter-strand hydrogen bonds also leading to a decrease of the life time.
Biotransformations of epiandrosterone (1), dehydroepiandrosterone (2), testosterone (3), progesterone (4) and pregnenolone (5) by Aspergillus tamarii MRC 72400 for 5 days have been reported and the results of these incubations have been compared with previously published data obtained with Aspergillus tamarii QM 1223. A. tamarii MRC 72400 showed higher Bayer–Villiger monooxygenase activities than A. tamarii QM 1223 did. Apart from pregnenolone (5), A. tamarii MRC 72400 metabolized these steroids in different ways. Incubation of epiandrosterone (1) afforded 3ß,11ß-dihydroxy-5?-androstan-17-one (6) (3%) and 3ß-hydroxy-17a-oxa-D-homo-5?-androstan-17-one (7) (9.5%). Incubation of dehydroepiandrosterone (2) afforded 3ß-hydroxy-17a-oxa-D-homoandrost-5-en-17-one (8) (28%), testolactone (9) (6%), 3ß,7ß-dihydroxyandrost-5-en-17-one (10) (13%) and 3ß,7?-dihydroxy- androst-5-en-17-one (11) (24%). Incubation of testosterone (3) afforded testolactone (9) (58%). Incubation of progesterone (4) also afforded testolactone (9), however in higher yield (86%). Incubation of pregnenolone (5) afforded 3ß-hydroxy-17a-oxa-D-homoandrost-5-en-17-one (8) (25%) and testolactone (9) (27%).
Several α-hydroxyamides with (2,6-dialkoxyphenoxy)methyl substituents have been prepared and their activities as antagonists of the M3 muscarinic receptor in guinea pig ileum have been evaluated. N-{1-[(Phenyl)methyl]piperidin-4-yl}-2-{2-[(2,6-dimethoxyphenoxy)-methyl]phenyl}-2-hydroxypropanamide and N-(1-[{6-amino-4-[(1-propylpiperidin-4-yl)methyl]pyridin-2-yl}methyl]piperidin-4-yl)-2-cyclopentyl-2-hydroxy-2-phenylacetamide were the most potent compounds prepared, the micromolar potency of the latter indicating that it may be worth further investigation.
Cholesteryl ester transfer protein (CETP), an enzyme which catalyses the transfer of cholesteryl ester from HDL to VLDL, is a promising target for discovery of novel antihyperlipidemic agents due to its pivotal role in HDL metabolism and reverse cholesterol transport. Quantitative structure activity relationship study of a series of CETP inhibitors was carried out using genetic function approximation to study various structural requirements for CETP inhibition. Various lipophilic, electronic, geometric and spatial descriptors were correlated with CETP inhibitory activity. Developed models were found predictive as indicated by their good r2pred values and satisfactory internal and external cross-validation results. Study reveals that lipophilicity (ClogP), with parabolic relationship, contributed significantly to the activity along with some electronic, geometric and quantum mechanical descriptors. The present study can be applied to future lead optimization of CETP inhibitors.
