[Inhibitors of alpha-amylase from plants--a possibility to treat diabetes mellitus type II by phytotherapy?].

Antidiabetics of plant origin are in common use. A proof of their effectiveness or their mode of action is often missing. The aim of this work was to review the knowledge about inhibitors of alpha-amylase from plants and to comment on the use in anti-diabetic treatment.

[The determination of pyridoxine hydrochloride (vitamin B6) according to European Pharmacopoeia 4.0].

Determination of pyridoxine hydrochloride according to the European Pharmacopoeia 4.0 In the Ph.Eur.

[Inhibition of the arachidonic acid cascade by aza-2-aryl-1,4-naphthoquinone derivatives].

Inhibition of the arachidonic acid cascade by aza-2-aryl-1,4-naphthoquinone derivatives To find more potent 5-lipoxygenase(LO)-inhibitors than the up to now studied 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-hydroxy-1,4-naphthoquinone derivatives the analogous aza-1,4-naphthoquinones 14, 15, 16/17 as well as the 3-bromo precursors 7, 8, 9/10 and 11 were synthesized. The naphtho[2,1-b][1,4]thiazin derivative 21 was included in this investigation as a quinone imine. Beside 5-LO inhibition the influence on 12-LO, COX-1 and cPLA2 was determined to investigate the selectivity of the compounds within the arachidonic acid cascade.

[Goldenrod--a classical exponent in the urological phytotherapy].

Herbal remedies based on goldenrod (Solidago virgaurea L.) have been well-tried for centuries in the treatment of urinary tract diseases. Investigations in molecular pharmacology could show new mechanisms responsible for the biological effect of natural product from goldenrod extracts.

[Influence of 2-aryl-3-halogen/3-hydroxy-1,4-naphthoquinones with salicylic and cinnamic acid partial structures on the arachidonic acid cascade].

Searching for more potent 5-lipoxygenase (LO) inhibitors one tert-butyl group of the selective 5-LO-inhibitor 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-hydroxy-1,4-naphthoquinone (1) was substituted by polar functions (-CHO, -COOH, -CH=CH-COOR, -CH2-CH2-COOR). At the same time the 5-LO selectivity of the new compounds within the arachidonic acid cascade was investigated. For this 12-LO- and COX-1-assays with activated human platelets were used.

[Methylated 2-aryl-1,4-naphtoquinone derivatives with diminished antioxidative activity].

Methylated 2-aryl-1,4-naphtoquinone derivatives with diminished antioxidative activity 2-(3,5-Di-tert-butyl-4-hydroxyphenyl)-3-hydroxy-1,4-naphthoquinone (1) is a selective 5-lipoxygenase (5-LOX) inhibitor possessing high antioxidative activity (AOA). In order to study the question if this activity corresponds to the mechanism of the 5-LOX inhibition (redox type 5-LOX inhibitor) the analogues 57-66 and their 3-methoxy derivatives 47-56 of the reference compound 1 were synthezised. These compounds are mono- and dimethylated within the benzoid molecular moiety which were tested for their 5-LOX inhibiting activity using human granulocytes and for their AOA by a chemiluminometric method.

Tributyrin-induced differentiation promotes apoptosis of LS 174T colon cancer cells in vitro.

Tributyrin (glyceryl tributyrate, TB) is known to induce malignant cells to differentiate followed by arrest of cell growth and death via apoptosis. We investigated the effects of TB on the distribution of cell cycle phases, differentiation as measured by alkaline phosphatase activity (ALP), and apoptosis of LS 174T colon cancer cells expressed by morphological changes, externalization of phosphatidylserine and stimulation of various caspases. TB (0.

Investigations of new lead structures for the design of selective estrogen receptor modulators.

Heterocyclic derivatives of (R,S)/(S,R)-1-(2-chloro-4-hydroxyphenyl)-2-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine (L1) were synthesized and tested for estrogen receptor binding. The selection of the heterocycles was based on theoretical consideration. (2R,3S)/(2S,3R)-2-(2-Chloro-4-hydroxyphenyl)-3-(2,6-dichloro-4-hydroxyphenyl)piperazine 2, (4R,5S)/(4S,5R)-4-(2-chloro-4-hydroxyphenyl)-5-(2,6-dichloro-4-hydroxyphenyl)-2-imidazoline 3, and 4-(2-chloro-4-hydroxyphenyl)-5-(2,6-dichloro-4-hydroxyphenyl)imidazole 4 possess a spatial structure with neighboring aromatic rings as is realized in hormonally active [1,2-diphenylethylenediamine]platinum(II) complexes.

Cutaneous inflammation and proliferation in vitro: differential effects and mode of action of topical glucocorticoids.

The nonhalogenated double ester of prednisolone, prednicarbate (PC), is the first topical glucocorticoid with an improved benefit/risk ratio verified clinically and in vitro. To evaluate if this is due to unique characteristics of this steroid, a new compound created according to an identical concept, prednisolone 17-ethylcarbonate, 21-phenylacetate (PEP), and the new halogenated monoester desoximetasone 21-cinnamate (DCE) were tested and compared to PC, desoximetasone (DM) and betamethasone 17-valerate (BMV). Isolated foreskin keratinocytes served for in vitro investigations of anti-inflammatory processes in the epidermis, fibroblasts of the same origin were used to investigate the atrophogenic potential.

Inhibitors of histone deacetylase suppress the growth of MCF-7 breast cancer cells.

Inhibitors of histone deacetylase are attracting increasing interest due to their influence on transcription, differentiation, and apoptosis. We have investigated two synthetic inhibitors 3 and 4 of histone deacetylase and the natural product inhibitor trichostatin A for their ability to suppress the growth of MCF-7 breast cancer cells and here present complete and improved synthetic procedures. The compounds show a dose dependent inhibition of growth with activities in the low micromolar and nanomolar range.

Effects of oral bromelain administration on the impaired immunocytotoxicity of mononuclear cells from mammary tumor patients.

The protease bromelain from pineapple was suggested for adjuvant therapy of malignant diseases. We studied immunological effects of an orally applied bromelain drug on 16 breast cancer patients in comparison with healthy donors. Bromelain was applied for 10 days with a daily dose of 3000 F.

[2-(3-Halogen-4-hydroxyphenyl)-1,4-napthoquinone derivatives from 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-analogs, potent 5-lipoxygenase inhibitors. 27. 1,4-Naphthoquinones].

A new simple and fast method for the synthesis of halogenated hydroxyphenyl naphthoquinones as potential 5-lipoxygenase (LOX) inhibitors is presented. While the aryl naphthoquinone 1, a potent 5-LOX inhibitor, with AlCl3 is debutylated to 2a and 2b, the oxidized cyclohexadienylidene derivative 3 reacts comparably by concomitant halogenation to 4a and with AlBr3 to 4b, respectively. As products of a side reaction of 6 with TiCl4 and BBr3 the tetracyclic benzo[b]naphthol[2,1-d]furan derivatives 8a and 8b are isolated.

Tributyrin induces growth inhibitory and differentiating effects on HT-29 colon cancer cells in vitro.

Tributyrin (TB) is a prodrug of butyrate known to induce tumor cells to differentiate. We examined its effects on cell growth, viability, cellular morphology and differentiation of HT-29 colon cancer cells in vitro, as reflected by the expression of CEA, E-cadherin and the induction of alkaline phosphatase activity. TB, applied in a stable emulsion, inhibited tumor cell proliferation in a reversible and dose-dependent manner (0.

Preclinical studies with prothymosin alpha1 on mononuclear cells from tumor patients.

The immunomodulating potential of the thymic protein prothymosin alpha1 (Pro alpha1) on the lymphocyte and monocyte directed antitumor reactions of melanoma and colorectal tumor patients in comparison with healthy controls were studied in vitro. On average, tumor patients showed lower NK- and LAK-cell activities than healthy controls, being associated with a lower adhesion capacity to tumor target cells. The NK-cell activity of the tumor patients was inversely related to the tumor stage.

Expression and modulation of the Lewis x antigen (CD15) on the T cell line Molt-4.

The T cell lines Molt-4 and H9 exhibited a characteristic distribution of the cell adhesion molecule Lewis x (CD15, lacto-N-fucopentanose III) showing an unusually broad peak by flow cytometry ranging from cells without CD15 to cells with high expression. The cytokines IL-1, IL-2, IFN-beta, IFN-gamma, and TNF-alpha, known to activate T cells, did not affect CD15 expression. However, phorbol myristate acetate and the thymic peptide extract Thymex-L were able to enhance both the number of CD15-positive cells and the median fluorescence.

Interleukin-2-activated killer cell activity in colorectal tumor patients: evaluation of in vitro effects by prothymosin alpha1.

The effects of prothymosin alpha1 (Pro alpha1) in combination with interleukin-2 (IL-2) on peripheral blood lymphocytes from 50 colorectal tumor patients at different stages were studied with respect to immunocytotoxicity, adhesion to cultured SW620 colon carcinoma cells, secretion of cytokines and expression of adhesion and surface marker molecules. On average, the patients showed lower natural killer (NK) cell activity than healthy donors, which was associated with a lower adhesion capacity to the tumor target cells. The NK cell activity of the patients was inversely related to the tumor stage.

A rapid and sensitive fluorometric screening assay using YO-PRO-1 to quantify tumour cell invasion through Matrigel.

A new quantitative assay for the study of tumour cell invasion in vitro is described. Employing the novel fluorescent dye YO-PRO-1, cells that penetrate Matrigel-coated transwells are counted on the basis of dye-bound cellular nucleic acid content. Following transmigration, the cells in the lower compartments are lysed by freezing in water.

Antimicrobial effects of oligoamines.

Twenty-four oligoamines belonging to six (1-6) structurally different types were tested in vitro for their antibacterial activity against 14 different bacterial species comprising a total of 187 strains. Ten compounds were able to inhibit growth of at least one strain at concentrations < or = 10 mumol/L. For three compounds, minimum inhibitory concentrations for some strains were even below 1 mumol/L.

Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XXX: Absorption, organ distribution, and excretion of the oligoamine (+)-(S,S)-1,4-bis-[4-(3-iodo-4-methoxyphenyl)-butylamino]-butane-2,3-di ol and its metabolites.

The pharmacokinetic behaviour of the 131-iodine-labelled title compound 3* and its metabolites in mice was investigated. A two phase, 1st order elimination profile was observed. The second phase is very slow leaving about 35% of radioactivity in the mice even 100 h after i.

Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XXIV: Interactions between oligosydnone imines and albumin or phospholipids.

Oligosydnone imines are strongly bound to albumin (alpha < 1%) in pure water. In saline, however, this effect is abolished (alpha approximately 80%). 4,4'-Propylene-bis-3-hexyl-sydnone-5-imine hydrochloride (1) moderately binds to phosphatidylcholine liposomes (PC, alpha approximately 34%).

Bromelain protease F9 reduces the CD44 mediated adhesion of human peripheral blood lymphocytes to human umbilical vein endothelial cells.

The thiol protease bromelain has been shown to remove T-cell CD44 molecules from lymphocytes and to affect T-cell activation. We investigated the effect of a highly purified bromelain protease F9 (F9) on the adhesion of peripheral blood lymphocytes (PBL) to human umbilical vein endothelial cells (HUVEC). Preincubation of the lymphocytes with F9 reduced the adherence to about 20% of unstimulated and to about 30% of phorbol-dibutyrate (P(Bu)2) stimulated lymphocytes.

New NO-donors with antithrombotic and vasodilating activities, VI: thiazole-2-nitrosimines.

24 new thiazole-2-nitrosimines were prepared and described by means of spectroscopical methods (NMR, IR, MS, UV). At pH 7 in cell free systems as well as in platelet rich plasma the compounds are stable against hydrolysis and do not react with the platelet glutathione. The chemical stability is underlined by the mass spectra: M+.

Conformational analysis and receptor modelling of m1 and m2 selective antagonists.

On the basis of an elaborate conformational analysis of m1- and m2-selective antagonists a respective pharmacophore was deduced. This then was introduced into models of the two muscarinic receptor subtypes. These models were constructed starting from bacteriorhodopsin as a template in accordance with alignment data and mutation experiments.

New NO-donors with antithrombotic activities and vasodilating activities, III: 3,4-disubstituted N-nitroso-5-sydnone imines.

38 title compounds have been synthesized. They bear a wide variety in substituents including alkyl-, aryl-, arylalkyl-, and styryl groups. The anti-platelet activities elucidated in the Born-test with collagen cover more than two orders of magnitude (IC50 = 0.