Comparison of HPLC, HPTLC, and In Silico Lipophilicity Parameters Determined for 5-Heterocyclic 2-(2,4-Dihydroxyphenyl)-1,3,4-thiadiazoles.

The 5-heterocyclic 2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles were obtained as potential biologically active compounds. Lipophilicity is one of the most important physicochemical properties of compounds and was already taken into account during the drug candidates design and development. The lipophilicity of compounds was determined using the computational (log P) and chromatography (log kw, RMw) methods. The experimental ones included the reverse-phase column high performance liquid chromatography RP (HPLC) with C8, C18, phosphatidylcholine (IAM), and cholesterol stationary phases and the thin layer chromatography (RP-HPTLC) with C8 and C18 stationary phases and various organic modifiers under the isocratic conditions. Descriptive statistics, correlation, and PCA analyses were used to compare the obtained results. For lipophilicity estimation of the tested compounds by HPTLC, dioxane and MeOH seem to be particularly beneficial as organic modifiers. The chromatographic lipophilicity parameters log kw (RMw) were well correlated and highly redundant (85%) compared with those calculated. Most compounds possess lipophilicity parameters within the recommended range for drug candidates.

Biological evaluation and molecular docking of novel 1,3,4-thiadiazole-resorcinol conjugates as multifunctional cholinesterases inhibitors.

Two series of novel 1,3,4-thiadiazole-resorcinol conjugates were efficiently synthesized and evaluated as cholinesterases inhibitors. N-Butyl- and N-chlorophenyl-5-amino-1,3,4-thiadiazol-2-yl)benzene-1,3-diols were identified as the most promising compounds of low nanomolar activity against AChE (IC50 = 29-76 nM) and moderate activity against BuChE. The inhibition mechanism studies proved that the compounds are mixed type inhibitors. The docking simulations showed great affinity of the compounds for both enzymes. The modelled amine derivatives exhibited a similar arrangement in the catalytic anionic site of AChE similar to that of tacrine. The thiadiazole ring interacted with Trp84 and the phenyl groups created π-π stacking interactions with the residue - Phe330. The compounds showed better inhibition of the in vitro self-induced Aß (1-42) aggregation than that compared with curcumin as well as antioxidant properties similar to those of quercetin. They exhibited metal ion chelating properties, acceptable cytotoxicity in vitro and favourable ADMET profile determined in silico.

Synthesis and antiproliferative activity of some N'-substituted 2,4-dihydroxybenzothiohydrazides.

The paper shows that new N'-substituted 2,4-dihydroxybenzocarbothiohydrazides are able to inhibit the in vitro proliferation of human tumor cell lines. The compounds were prepared by the reaction of sulfinylbis[(2,4-dihydroxyphenyl)methanethione] (STB) or its analogs with the hydrazines. The panel of N'-substitution included aryl, pyridinyl and pyrimidinyl rings. The highest antiproliferative activity for N'-(4-(4-chlorophenyl)-6-(trifluoromethyl)pyrimidin-2-yl)-5-ethyl-2,4-dihydroxybenzothiohydrazide (5b) was found. The antiproliferative potency of some compounds was similar to that of cisplatin. Analogs with the Et substituent on benzenediol moiety displayed higher potency than with the unsubstituted one. The influence of N'-substitution on antiproliferative activity of compounds was discussed.

NMR QSAR model for the analysis of 4-(5-arylamino-1,3,4-thiadiazol-2-yl)benzene-1,3-diols.

We have developed a NMR data quantitative structure-activity relationship NMR-QSAR model based on (1)H- and (13)C-NMR experimental spectral data of 4-(5-arylamino-1,3,4-thiadiazol-2-yl)benzene-1,3-diols. Compounds show in-vitro antiproliferative activity against some human cancer cell lines. Two-parameter equations obtained by the multiple linear regression procedure showed that chemical shifts of the protons of hydroxyl groups and carbon atoms of the 1,3,4-thiadiazole ring are the decisive descriptors of inhibition interactions of the compounds. The models gave leave-one-out (LOO) cross-validation ranges from 78% to 93%. The obtained NMR-QSAR equations provide a rapid, reliable, and simple way for predicting the antiproliferative activity of N-substituted 4-(5-amino-1,3,4-thiadiazol-2-yl)benzene-1,3-diols.

Rapid and simple high-performance liquid chromatographic determination of felbamate in serum.

An isocratic high-performance liquid chromatographic method for the quantitation of felbamate in serum is presented. The method is based on protein precipitation with acetonitrile and reversed-phase chromatography with spectrophotometric detection at 210 nm. The separation was performed on a Nova-Pak C18 column and the mobile phase consisted of acetonitrile-water (1:4, v/v). Phenobarbital was applied as an internal standard. The assay was linear over the concentration range 0.5-200.0 microg/ml (r = 0.9999). Intra-day and inter-day precision expressed by relative standard deviation is less than 3%. The percentage of recovery was 98.63 +/- 2.47. The method is suitable for drug level monitoring and for pharmacokinetic studies.

LC determination of moclobemide and three metabolites in plasma.

Moclobemide and three metabolites were quantified using 1 ml of plasma and solid-phase extraction with Bakerbond CN column after the addition of nadolol as the internal standard (I.S.). Separation and detection the analysed substances were achieved isocratically with acetonitrile-methanol-0.067 M phosphate buffer pH 2.65-0.4% triethylamine (12.7:1.9:85:0.4, v/v/v/v), a Nova-pak C(8) column and UV detection at 230 nm. The lower limits of quantitation for moclobemide was 10 ng ml(-1), for M1 (Ro 16-3177)-8 ng ml(-1), for M2 (Ro 12-5637)-10 ng ml(-1) and for M3 (Ro 12-8095)-15 ng ml(-1) (as the metabolites). Accuracies calculated of three concentrations in each of three separate runs were between 84.55 and 93.68 for moclobemide, 83.28 and 92.30 for M1, 86.31 and 92.66 for M2 and 88.42 and 93.40 for M3. Precision data within day were between 5.71 and 7.50 for moclobemide, 2.91 and 6.58 for M1, 4.98 and 6.40 for M2 and 0.94 and 4.73 for M3.

Applications of derivative UV spectrophotometry for the determinations of cetirizine dihydrochloride in pharmaceutical preparations.

A method for the determination of cetirizine dihydrochloride in pharmaceuticals by first-, second-, third- and fourth- order derivative spectrophotometry is described, using "peak-peak" (P-P), and "peak-zero" (P-0) measurements. The calibration curves are linear within the concentration range of 7.5-22.5 microg ml(-1) for cetirizine dihydrochloride. The procedure is simple, rapid and the results are reliable.