ABSTRACT
Advantages associated with the transdermal delivery route are well documented, but in the past scientists have concentrated primarily on means of decreasing the barrier function of the skin for improved permeability. Pro-drugs, which possess more favourable physicochemical properties for improved transdermal permeability may have considerable potential. These have been considered in the past but recent information concerning structure activity relationships in dermal penetration has prompted increased interest. During this study, N-methyl (2), N-ethyl (3) and N-(2-hydroxyethyl) carbamazepine (4) analogues were synthesised for transdermal evaluation.
Subject(s)
Carbamazepine/analogs & derivatives , Carbamazepine/administration & dosage , Administration, Cutaneous , Carbamazepine/chemistry , Chromatography, High Pressure Liquid , Female , Humans , In Vitro Techniques , Permeability , Skin Absorption , Solubility , Transition TemperatureABSTRACT
Resting cells of the yeast Rhodosporidium toruloides (UOFS Y-0471) were immobilised in calcium alginate beads for the enantioselective kinetic resolution of racemic-1,2-epoxyoctane. The initial activity exhibited by immobilised cells was almost 50% lower than that of the free counterpart but was extremely stable when compared to the free cells. The concentration of the immobilised biomass had no effect on apparent enzyme activity but did lead to a decrease in single cell activity. An increase in both the alginate and CaCl2 concentrations used for bead preparation led to a decrease in enzyme stability. An increase in the alginate concentration led to an increase in bead diameter. The stoichiometric equation for cross-linking of alginate was only obeyed when CaCl2 concentrations higher than 0.4 M were utilised for bead preparation.
Subject(s)
Basidiomycota/growth & development , Basidiomycota/metabolism , Cell Culture Techniques/methods , Epoxide Hydrolases/metabolism , Epoxy Compounds/metabolism , Extracellular Matrix/physiology , Glucuronic Acid/physiology , Octanes/metabolism , Alginates , Cells, Immobilized/physiology , Enzyme Activation , Enzyme Stability , Hexuronic Acids , Kinetics , Microspheres , StereoisomerismABSTRACT
Yeast strains (410) from more than 45 different genera were screened for the enantioselective hydrolysis of nitro substituted styrene oxides. These strains included 262 yeasts with known epoxides hydrolase activity for various other epoxides. Epoxide hydrolase activity for p-nitrostyrene oxide (pNSO) (177 strains) and m-nitrostyrene oxide (mNSO) (148 strains) was widespread in the yeasts, while activity for o-nitrostyrene oxide (oNSO) was less ubiquitous (22 strains). The strains that displayed enantioselectivity in the hydrolysis of one or more of the nitro substituted styrene oxides (35 strains) were also screened against styrene oxide (SO). Rhodosporidium toruloides UOFS Y-0471 displayed the highest enantioselectivity for pNSO (ee 55%, yield 35%) while Rhodotorula glutinis UOFS Y-0653 displayed the highest enantioselectivity for mNSO (ee > 98%, yield 29%), oNSO (ee 39%, yield 19%) and SO (ee > 98%, yield 19%). (R)-Styrene oxide was preferentially hydrolysed to the corresponding (R)-diol with retention of configuration at the stereogenic centre. In the case of the nitro substituted styrene oxides the absolute configurations of the remaining epoxides and the formed diols were not established.
Subject(s)
Epoxide Hydrolases/classification , Epoxide Hydrolases/metabolism , Epoxy Compounds/metabolism , Yeasts/classification , Yeasts/enzymology , Catalysis , Cells, Cultured , Epoxide Hydrolases/chemistry , Epoxy Compounds/chemistry , Epoxy Compounds/classification , Species Specificity , Stereoisomerism , Yeasts/chemistryABSTRACT
The in vitro antimalarial activity of a series of 2- and 8-trifluoromethyl- and 2,8-bis(trifluoromethyl)quinoline-4-(5-pyrimidino) and N4-ethyl-5-nitroimidazolo)methylene ketones was assessed against the chloroquine-sensitive strain (D10) of Plasmodium falciparum. Although the in vitro antimalarial activity of these compounds is more or less of the same order of magnitude, derivatives containing two trifluoromethyl groups achieve a slightly higher in vitro activity than compounds with one trifluoromethyl group, with 2,8-bis(trifluoromethyl) quinoline-4-(N4-ethyl-5-nitroimidazolo) methylene and 2,8-bis(trifluoromethyl) quinoline-4-(5-pyrimidino) ketones showing IC50 of 4.8 and 5.2 micrograms/ml, respectively. These compounds seem to bind to DNA by intercalation.
Subject(s)
Antimalarials/pharmacology , Quinolines/pharmacology , Animals , Binding, Competitive/drug effects , Chloroquine/pharmacology , DNA/drug effects , DNA/metabolism , Ethidium/metabolism , Intercalating Agents/chemical synthesis , Intercalating Agents/pharmacology , L-Lactate Dehydrogenase/metabolism , Plasmodium falciparum/drug effects , Plasmodium falciparum/enzymology , Structure-Activity RelationshipABSTRACT
A range of N-substituted isoindolin-1-ones was prepared and their potential as novel antimicrobial agents was investigated. MIC values for active compounds were determined and reported.
Subject(s)
Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/pharmacology , Indoles/chemical synthesis , Indoles/pharmacology , Anti-Bacterial Agents , Anti-Infective Agents/chemistry , Aspergillus/drug effects , Candida albicans/drug effects , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Indoles/chemistry , Microbial Sensitivity TestsABSTRACT
The solubility of chlorthalidone in 16 solvent systems was determined in the absence and presence of different amounts of beta-cyclodextrin (beta-CD). Chlorthalidone (CT) was shown to be more soluble in hydrophilic organic solvents, with the highest solubility in ethylacetate (EtOAc) saturated with water. The solubility of CT in water, butanol, octanol, and dichloromethane (DCM) was enhanced by the addition of beta-cyclodextrin. The enantioselective partitioning of CT between water and EtOAc, DCM, butan-1-ol, butan-2-ol, and octan-1-ol was determined in the presence of beta-CD at pH 5, 7, and 9. According to the results, both the solubility and partitioning properties of CT are affected by beta-CD in aqueous solution. It was also shown that the solubility of the individual enantiomers differs in the presence of beta-CD.
Subject(s)
Chlorthalidone/chemistry , Cyclodextrins/pharmacology , beta-Cyclodextrins , Solubility , Stereoisomerism , Water/chemistryABSTRACT
Trimethoprim undergoes thermally and photochemically catalyzed hydrolysis or oxidation to give rise to at least five products. The structures of these compounds were determined by physical methods and it was found that the resonance of C-5 in the 13C NMR spectrum is indicative of the substitution pattern of the resultant amino hydroxy pyrimidines.