Biotransformations of monoterpenes by photoautotrophic micro-organisms.

Monoterpenes are widely used in food technology, cosmetic and pharmaceutical industries and as compounds of agricultural importance. It is known that compounds comprising this class can be transformed by a variety of organisms, namely by: bacteria, fungi, yeasts, plants or isolated enzymes. Biotransformations, as one of the most important tools of green chemistry, allow obtaining new products using whole cells of micro-organisms or isolated enzymes in mild reaction conditions. Therefore, biotransformations of monoterpenes, by different type of reaction such as: epoxidation, oxidation and stereoselective hydroxylation, resulted in the production of so desired, enantiomerically defined compounds that can be advised as natural seem to be interesting. Bearing in mind that such processes are carried out also by easy to maintain, photoautotrophic micro-organisms cultivated at large scale, this paper is focused on biotransformations of acyclic, monocyclic and bicyclic monoterpenes by freshwater or haliphylic cyanobacteria and microalgae on the way of mainly stereoselective hydroxylation. Moreover, aspects of potential industrial application of obtained products in medicine, perfume, cosmetics and food industry are discussed.

A role of GABA analogues in the treatment of neurological diseases.

gamma-Amino butyric acid is an extremely important inhibitory neurotransmitter in the mammalian central nervous system and is essential for the overall balance between neuronal excitation and inhibition. It is well documented that GABA deficiency is associated with several important neurological disorders such as Huntington's chorea, Parkinson's and Alzheimer's disease and other psychiatric disorders, like anxiety, depression, pain, panic, or mania. Although, it is known that increasing the brain concentration of GABA prevents convulsions, the high polarity and flexible structure of this compound are probably responsible for its inefficiency as an anticonvulsant when administered orally or intravenously. To resolve this problem, GABA analogues are being designed. Over recent years, there has been increasing interest in the synthesis and pharmacological effect of new GABA derivatives, which can be considered as potent drugs in the treatment of neurodegenerative disorders.

Effects of a carane derivative local anesthetic on a phospholipid bilayer studied by molecular dynamics simulation.

Molecular dynamics (MD) simulations of two hydrated palmitoyloleoylphosphatidylcholine (POPC) bilayers each containing eight carane derivative (KP-23) local anesthetic (LA) molecules in neutral (POPC-LA) or protonated (POPC-LAH) forms were carried out to investigate the effect of KP-23 and its protonation on the bilayer. 3-ns trajectories were used for analyses. A pure POPC bilayer was employed as a reference system. In both POPC-LA and POPC-LAH systems a few KP-23 molecules intercalated into the bilayer and moved near the bilayer/water interface. They were located on the hydrophobic core side of the interface in the POPC-LA bilayer, but on the water phase side in the POPC-LAH bilayer. The order of the POPC chains was higher in the POPC-LA bilayer than in the pure POPC bilayer and was lower in the POPC-LAH bilayer. Interactions between polar groups of KP-23 and POPC or water were responsible for a lower hydration of POPC headgroups in POPC bilayers containing KP-23 than in the pure POPC bilayer. KP-23 molecules were found to form aggregates both in POPC-LA and POPC-LAH bilayers. Due to higher amphiphilicity of LAH, the LAH aggregate was more micelle-like and larger than the LA one. The results demonstrate the rapid timescales of the initial processes that take place at and near the bilayer interface as well as details of the atomic level interactions between local anesthetic and the lipid matrix of a cell membrane.

Comparative investigations of hydroxyamine carane derivative and its R,S-diastereoisomers with strong local anesthetic activity.

Our previously conducted pharmacological screening led as to the discovery of the strong local anesthetic activity of the compound designated as KP-23. Earlier crystallographic studies revealed that the compound KP-23 crystallized in diastereoisomeric form in lowest symmetry. The aim of these comparative investigations was to evaluate anesthetic activity of KP-23 and its R,S-diastereoisomers, which were synthesized at the Institute of Organic Chemistry, Biochemistry and Biotechnology, Wroclaw University of Technology.

Propranolol analogs containing natural monoterpene structures: synthesis and pharmacological properties.

A few derivatives of natural, bicyclic monoterpenes, which are propranolol analogs, were synthetized. Those compounds were studied pharmacologically in order to determine their toxicity, antiarrhythmic activity in selected experimental models of arrhythmia, the local anesthetic effect and influence on the cardiovascular system. The tested compounds showed a less potent or similar toxicity towards reference drugs, were devoid of an antiarrhythmic activity in the model of barium arrhythmia, yet some of them (compounds 9 and 12) increased the arrhythmogenic dose of strophanthin. All the compounds studied had a local anesthetic effect stronger than lidocaine in infiltration anesthesia, and compound 8--also in surface anesthesia.

Synthesis and local anesthetic and circulatory actions of aminoesters and hydroxyamine monoterpene derivatives.

Esters of N,N-diethylaminoacetic acid and hydroxyamines, obtained from structurally different natural monoterpenes, were pharmacologically examined. It was proved that salts of the obtained compounds had local anesthetic properties in infiltration anesthesia, compounds 9, 6 and 8 having been more potent than lidocaine. Compounds 7-9 slightly increased the arrhythmogenic dose, and compound 12 - the lethal dose of strophanthin. All the examined compounds transiently decreased the arterial blood pressure and displayed a cardiopressive activity.

Synthesis and some pharmacological properties of 1,2-amino ethers with natural monoterpene structures.

Synthesis and physicochemical and pharmacological properties of 10 analogs of 2-[2-(6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)ethoxy]N, N-diethylamino ethane (3) have been described. The compounds possess toxicity close to or lower than the parent compound--myrtecaine, have no antiarrhythmic activity but some of them (15, 16, 22, 24), similarly as compound 3, show quite strong local anesthetic action.