ABSTRACT
The antihypertensive activity of the medicinal plant Hancornia speciosa has been previously demonstrated by us, being the activity ascribed to polyphenols and cyclitols like l-(+)-bornesitol. We herein evaluated the stability of the bioactive marker bornesitol submitted to forced degradation conditions. Bornesitol employed in the study was isolated from H. speciosa leaves. An UHPLC-ESI-MS/MS method was developed to investigate bornesitol stability based on MRM (Multiple Reaction Monitoring) acquisition mode and negative ionization mode, employing both specific (m/z 193â¯ââ¯161â¯Da) and confirmatory (m/z 193â¯ââ¯175â¯Da) transitions. A gradient elution of 0.1% formic acid in water and acetonitrile was performed on a HILIC column. The method was validated and showed adequate linearity (r2â¯>â¯0.99), selectivity, specificity, accuracy, and precision (RSDâ¯<â¯2.9%). The method was robust for deliberate variations on dessolvation temperature, but not for changes in the flow rate and dessolvation gas. The results from the stability studies allowed us to classify bornesitol as labile for acidic and alkaline hydrolysis, but as very stable for oxidative and neutral hydrolysis exposure. Bornesitol was categorized as practically stable under photolysis degradation, whereas a considerable reduction on its contents was induced by metal ions and thermolysis exposure. Degraded samples from neutral hydrolysis and thermolysis were assayed in vitro for ACE inhibition and showed a substantial decrease in biological activity as compared to intact bornesitol. myo-Inositol was identified as the major degradation products in both matrices. This is the first report on bornesitol stability under different stress conditions and the obtained data are relevant for the development and quality control of standardized products from H. speciosa leaves.
Subject(s)
Apocynaceae/chemistry , Chromatography, High Pressure Liquid/methods , Cyclitols , Mass Spectrometry/methods , Peptidyl-Dipeptidase A/drug effects , Angiotensin-Converting Enzyme Inhibitors/analysis , Angiotensin-Converting Enzyme Inhibitors/chemistry , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Biomarkers/analysis , Biomarkers/chemistry , Cyclitols/analysis , Cyclitols/chemistry , Cyclitols/pharmacology , Drug Stability , Limit of Detection , Linear Models , Peptidyl-Dipeptidase A/metabolism , Plant Extracts/chemistry , Reproducibility of ResultsABSTRACT
A small library of compounds was prepared by a combination of toluene dioxygenase (TDO)-catalyzed enzymatic dihydroxylation and copper(I)-catalyzed Hüisgen cycloaddition. Some compounds were obtained by coupling an alkyne and a conduritol derivative, while more complex structures were obtained by a double Hüisgen reaction of a dialkyne and two molecules of the cyclitol. The compounds were fully characterized and subjected to preliminary biological screening.
Subject(s)
Cyclitols/chemical synthesis , Cyclitols/pharmacology , Small Molecule Libraries/chemical synthesis , Small Molecule Libraries/pharmacology , Animals , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Cell Proliferation/drug effects , Cells, Cultured , Cyclitols/chemistry , Cycloaddition Reaction , Immunosuppressive Agents/chemical synthesis , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/pharmacology , Male , Mice , Mice, Inbred C57BL , Molecular Structure , Small Molecule Libraries/chemistry , Triazoles/chemical synthesis , Triazoles/chemistry , Triazoles/pharmacologyABSTRACT
Cylitol L-(+)-bornesitol is regarded as a bioactive constituent from Hancornia speciosa leaves, a plant species traditionally used in Brazil to treat diabetes and hypertension. We report a simple HPLC-DAD method for the quantification of bornesitol in extracts from H. speciosa leaves, after derivatization with p-toluenesulfonyl chloride, using pentaerythritol as internal standard. A gradient of methanol, acetonitrile and water was employed for elution on an ODS column and detection was set up at a wavelength of 230 nm. The method was selective and linear over the range 60.4-302.0 µg/ml with r² of 0.9981, and showed satisfactory precision for intra-day (RSD=2.37%) and inter-day (RSD=3.17%) assays. The recovery varied between 92.3% and 99.9% and the limits of quantification and detection were respectively 5.00 and 1.67 µg/ml. The method was applied to quantify bornesitol in extracts from H. speciosa leaves of different specimens.
Subject(s)
Apocynaceae/chemistry , Chromatography, High Pressure Liquid/methods , Cyclitols/analysis , Plant Extracts/chemistry , Tosyl Compounds/chemistry , Cyclitols/chemistry , Drug Stability , Linear Models , Plant Leaves/chemistry , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
The palladium catalyzed cross-coupling reaction of phenyltrifluoroborate with a chemoenzymatically derived bromoazidoconduritol, combined with 1,3-dipolar cycloaddition, with a variety of alkynes is described. Fourteen new compounds were synthesized in moderate to good yields. The click chemistry reaction can be effected by using sodium ascorbate and CuSO(4) · 5H(2)O as catalyst in toluene-H(2)O at room temperature.
Subject(s)
Biocatalysis , Click Chemistry/methods , Cyclitols/chemistry , Palladium/chemistry , Cyclitols/chemical synthesis , Dioxygenases/metabolism , Pseudomonas putida/enzymologyABSTRACT
The first syntheses of two deoxythiocyanocyclitols (4-deoxy-4-thiocyano-L-chiro-inositol and deoxythiocyanoconduritol F) and two deoxysulfonylcyclitol acetals are reported by a chemoenzymatic enantioselective route. The compounds were prepared by a sequence of enzymatic and ruthenium-catalyzed dihydroxylations, and the results were studied regarding reaction conditions and co-catalyst for different derivatives. The new compounds were included in a minilibrary of deoxygenated cyclitols and evaluated for their capacity to influence the feeding behavior of Epilachna paenulata (Coleoptera: Coccinellidae), a common pest of the Curcubitaceae crops.