Cytotoxic and HIF-1alpha inhibitory compounds from Crossosoma bigelovii.

Cytotoxicity-guided fractionation of an organic solvent extract of the plant Crossosoma bigelovii led to the discovery of a new strophanthidin glycoside (1) and two new 2-methylchromone glycosides (2 and 3). Also isolated were the known chromones eugenin and noreugenin, the indole alkaloid ajmalicine, the dibenzylbutane lignan secoisolariciresinol, the dibenzylbutyrolactone lignan matairesinol, and the furanone 5-tetradec-5-enyldihydrofuran-2-one. Further investigation into the biological properties of strophanthidin glycosides revealed a connection between inhibition of HIF-1 activation and the glycosylation of the genin. This work is the first published study of the bioactive phytochemicals of the family Crossosomataceae.

Subzero nonfreezing storage of rat hepatocytes using modified University of Wisconsin solution (mUW) and 1,4-butanediol. I- effects on cellular metabolites during cold storage.

Various cryopreservation techniques have been investigated to extend the storage of isolated hepatocytes; however, most have a reduced viability after rewarming due to ice crystal formation. Subzero nonfreezing conditions could theoretically reduce organ metabolism without damage due to ice crystal formation. In the present work we evaluated the viability and metabolic parameters of isolated rat hepatocytes preserved in subzero nonfreezing condition. Cell suspensions were maintained in modified University of Wisconsin (mUW) solution using 8% - ,4-butanediol as cryoprotectant, up to 120 h at -4 masculineC. The time course evolution of hepatocytes viability were measured by LDH release and propidium iodide assay. The cellular concentrations of glutathione, ATP, glycogen and the lactate production during cold storage were also determined. Finally, results were compared with conventional hypothermic storage at 0 masculineC in mUW solution without cryoprotectant. After 5 days of subzero storage, we found an improvement in the ability of rat hepatocytes to maintain the metabolic resources in comparison with the cold preserved group.

Synthesis and trypanocidal activity of 1,4-bis-(3,4,5-trimethoxy-phenyl)-1,4-butanediol and 1,4-bis-(3,4-dimethoxyphenyl)-1,4-butanediol.

Chagas' disease is endemic in Central and South American countries. Specific chemotherapy with nifurtimox or benznidazole has been recommended for treatment of recent infection but they have limited efficacy. The natural products veraguensin (1) and grandisin (2) have shown potent in vitro activity against trypomastigote parasite (Y strain) with IC(50) 2.3 microM (1) and 3.7 microM (2). We report herein the synthesis and in vitro trypanocidal evaluation of symmetrical and unsymmetrical 1,4-diaryl-1,4-diol derivatives as potential trypanocidal analogs of natural compounds 1 and 2. Among the synthesized products, compounds 1,4-bis-(3,4,5-trimethoxyphenyl)-1,4-butanediol (6a) and 1,4-bis-(3,4-dimethoxyphenyl)-1,4-butanediol (6b) showed better activity against Trypanosoma cruzi trypomastigotes with IC(50) 100 and 105 microM (Y strain), respectively, and 110 microM (Bolivia strain) for both compounds. However, the most active compound of this series was 1,4-bis-(3,4-dimethoxyphenyl)butane-1,4-dione (7b) with IC(50) 10 and 200 microM against Y and Bolivia strains, respectively.

Influence of the morphology of poly(EGDMA-co-HEMA) on the chemical modifications and retention of O-phosphothreonine.

The influence of the morphology of ethylene glycol dimethacrylate-hydroxyethyl methacrylate copolymer [poly(EGDMA-co-HEMA)] base support to obtain different Fe(3+)-containing sorbents and their properties in retention of O-phosphothreonine [Thre(P)] is examined in this paper. Three base supports poly(EGDMA-co-HEMA) (I-III) were obtained using different quantities of initiator in suspension polymerization reactions. These products were submitted to chemical modifications using 1,4-butanediol diglycidyl ether (BDGE) in activation reactions and different chelating agents (iminodiacetic acid, IDA; disodium ethylenediamine tetraacetate, EDTA; and hexamethylenediamine tetrapropanoic acid, HMDTP) in coupling reactions to attain Fe(3+)-containing sorbents. Properties such as specific surface area (S(s)), specific pore volume (V(p)), scanning electron microscopy (SEM), IR spectroscopy, quantity of functional groups (oxirane and carboxyl), amount of chelated metal ion, ligand occupation (L), swelling studies as well as quantity of O-phosphoamino acid retained were used as comparative parameters for matrices. In general, the derivatization reactions proved to be more efficient when higher S(s) of macropores (50-400,000 nm) were available in the matrix. In our case, it was observed when highest percentage of initiator was used. On the other hand, the effect of accessibility of surface area on the yield of coupling reactions was noticed when comparing the different chelating agents since the number of carboxyl groups present in products was higher when the molecular size of the chelating agent was lower. Although all Fe(3+)-containing sorbents resulted efficient to retain Thre(P), the values of retention of the amino acid were slightly higher when IDA-containing matrices were used irrespective of the quantity of metal chelated. This could be probably due to the fact that the IDA ligand could be bounded to the matrix in sites that though accessible for the center of adsorption were hard for Thre(P) to access.

Stereochemical assignment of naturally occurring 2,3-epoxy-2-methylbutanoate esters.

A method to determine the absolute configuration of 2,3-epoxy-2-methylbutanoate ester residues in natural products is presented, based on (i) the reduction of the ester function to yield a 2-methyl-1,2-butanediol, (ii) esterification of the obtained primary alcohol with either (R)-(+)- or (S)-(-)-Mosher's acid to afford the corresponding Mosher's ester, and (iii) 1H-NMR spectral comparison of the final product with that of the Mosher's esters prepared from 2-methyl-1,2-butanediols of known stereochemistry.