Investigation of the antibacterial activity of 3-O-octanoyl-(-)-epicatechin.

AIMS: To measure antibacterial activity of the semi-synthetic flavonoid 3-O-octanoyl-(-)-epicatechin and investigate the mechanism of action. METHODS AND RESULTS: MICs determined by the broth microdilution method were 50 microg ml(-1) for beta-lactam sensitive and resistant Staphylococcus aureus, and 100 microg ml(-1) for vancomycin sensitive and resistant enterococci. In time-kill studies, 100 microg ml(-1) 3-O-octanoyl-(-)-epicatechin reduced colony forming unit numbers of antibiotic sensitive and methicillin-resistant Staph. aureus below detectable levels within 120 min. Bacterial aggregation was not observed when cells exposed to 3-O-octanoyl-(-)-epicatechin were examined by light microscopy. It was also shown that 50 microg ml(-1) 3-O-octanoyl-(-)-epicatechin is capable of reducing colony forming unit numbers of high cell density Staph. aureus populations by 80-fold within 60 min incubation, and inducing leakage of 50% of their internal potassium within just 10 min. CONCLUSIONS: 3-O-Octanoyl-(-)-epicatechin is active against Gram-positive bacteria, has bactericidal activity against both antibiotic sensitive and resistant strains, and is likely to exert its primary antibacterial effect by damaging the cytoplasmic membrane. SIGNIFICANCE AND IMPACT OF THE STUDY: 3-O-Octanoyl-(-)-epicatechin has significant antibacterial activity and additional structural modification and/or formulation studies may allow this to be potentiated.

Synthesis and cancer antiproliferative activity of new histone deacetylase inhibitors: hydrophilic hydroxamates and 2-aminobenzamide-containing derivatives.

New series histone deacetylase inhibitors comprising a hydroxamic acid or 2-aminobenzamide group as a zinc-chelating function were synthesized and evaluated for antiproliferative activities against a panel of human cancer cells. The 2-aminobenzamide series inhibitors generally had the potency in cell growth inhibitions comparable to that of MS-275. Among them, the compound having a (3,4-difluorobenzyl)(2-hydroxyethyl)amino group at one end and a 2-aminobenzamide group at the other of molecule showed the most promising profile as an anticancer drug candidate, since it had a comparatively low toxicity as did MS-275 against a normal fibroblast cell CCD-1059SK. Additionally, the derivative exhibited a high recovery in human plasma stability test.

Inhibition of green tea catechins against the growth of cancerous human colon and hepatic epithelial cells.

The ability of (-)-epicatechin (EC), (-)-epigallocatechin (EGC) and (-)-epigallocatechin gallate (EGCG) to inhibit the growth of HCT 116 colorectal and Hep G2 hepatocellular carcinoma cells was examined by MTT and clonogenic assays (CA). The respective catechins inhibited the growth of HCT 116 more strongly than Hep G2. In MTT assay, IC(50) values of EGC and EGCG against HCT 116 grew smaller on prolongation of the exposure times of the cells to the catechins. In CA, however, these two catechins had IC(50) values ranging between 7.6+/-0.4 and 11.2+/-0.5 microM against the same cells regardless of the exposure times. EC showed much weaker growth inhibitions relative to the two aforementioned catechins.

Inhibitory effects of 6-O-acylated L-ascorbic acids possessing a straight- or branched-acyl chain on Epstein-Barr virus activation.

6-O-Acylated L-ascorbic acids possessing a straight- or branched-acyl chain of varying length from C(4) to C(18) have been synthesized and evaluated their anti-tumor promoting effects on the activation of the Epstein-Barr virus early antigen. The derivatives having a straight- or branched-acyl chain of C(6) to C(11) carbon atoms exhibited marked effects.

Antitumor promoting activities of 3-O-acyl-(-)epigallocatechins.

As an exploratory investigation of antitumor promoting compounds, 3-O-acyl-(-)-epigallocatechins possessing a straight-, branched-, phenyl-inserted- or 1,4-phenylene-inserted-acyl chain of varying length from C4 to C18 were synthesized and evaluated their inhibitory effects against the activation of the Epstein-Barr virus early antigen (EBV-EA). It was indicated that the epigallocatechin derivatives having the straight- or branched-acyl chain of C8 to C11 carbon atoms achieve marked effects.

Absolute stereochemistry of gastric antisecretory compound P371A1 and its congener P371A2 from streptomyces species P371.

Absolute configurations of the gastric antisecretory compound P371A1 (1) and its congener P371A2 (2) from Streptomyces sp. P371 were determined on the basis of identification of the methyl glycosides 9, 10, and 11 obtained by the acid degradation of 1 and 2, as well as application of the modified Mosher method to the P371A2 C-glycoside MTPA esters 7 and 8 and observation of the excitation chiralities in the P371A2 C-glycoside benzoate derivatives 5 and 6.

Novel angucycline compound with both antigastrin- and gastric mucosal protective-activities.

An angucycline series compound P371 A1 (1) from Streptomyces sp. P371 was established to have a novel structure comprising an ureido group at one of four sugar units on the basis of 2D NMR techniques. 1 exhibited an inhibitory activity against the pentagastrin-stimulated acid secretion as well as protective activities against HCl/ethanol- and indomethacin-induced gastric lesions.

Fungal metabolites. X. The effect of peptide antibiotics, trichosporin-Bs, on the respiratory activity of mitochondria.

The effect of the trichosporin-Bs, peptide antibiotics, on the respiration of mitochondria was investigated. Trichosporin-Bs stimulated the respiratory rate of state 4 rat liver mitochondria in a dose-dependent manner. The maximum respiratory rate obtained by trichosporin-Bs was essentially the same as for 2,4-dinitrophenol and SF6847. Trichosporin-B-VIb released oligomycin-inhibited respiration of mitochondria. This means that trichosporin-Bs are uncouplers of oxidative phosphorylation. The stimulatory effect of trichosporin-B-VIb, a component of trichosporin-Bs, on mitochondrial respiration was increased by inorganic phosphate but not by other permeant anions studied. These results suggest that the stimulation of mitochondrial respiration by trichosporin-B-VIb is mediated by the same mechanism as is operating in the case of hypelcins and alamethicins. Furthermore, the relative potencies of trichosporin-Bs on the mitochondrial respiration and their relative hydrophobicities were examined. A clear relationship was observed between the uncoupling potencies of trichosporin-Bs and their relative hydrophobicities.

Acyclic monoterpene primary alcohol:NADP+ oxidoreductase of Rauwolfia serpentina cells: the key enzyme in biosynthesis of monoterpene alcohols.

Acyclic monoterpene primary alcohol:NADP+ oxidoreductase, a key enzyme in the biosynthesis of monoterpene alcohols in plants, is unstable and has been only poorly characterized. However we have established conditions which stabilize the enzyme from Rauwolfia serpentina cells, and then purified it to homogeneity. It is a monomer with a molecular weight of about 44,000 and contains zinc ions. Various branched-chain allylic primary alcohols such as nerol, geraniol, and 10-hydroxygeraniol were substrates, but ethanol was inert. The enzyme exclusively requires NADP+ or NADPH as the cofactor. Steady-state kinetic studies showed that the nerol dehydrogenation proceeds by an ordered Bi-Bi mechanism. NADP+ binds the enzyme first and then NADPH is the second product released from it. Gas chromatography-mass spectrometric analysis of the reaction products showed that 10-hydroxygeraniol undergoes a reversible dehydrogenation to produce 10-oxogeraniol or 10-hydroxygeranial, which are oxidized further to give 10-oxogeranial, the direct precursor of iridodial. The enzyme has been found to exclusively transfer the pro-R hydrogen of NADPH to neral. The N-terminal sequence of the first 21 amino acids revealed no significant homology with those of various other proteins including the NAD(P)(+)-dependent alcohol dehydrogenases registered in a protein data bank.