Antimycobacterial and cytotoxicity activities of free and liposome-encapsulated 3-(4'-bromo[1,1'-biphenyl-4-yl)-3-(4-bromo-phenyl)-N,N-dimethyl-2-propen-1-amine

The antimycobacterial activity of 3-(4'-bromo[1,1'-biphenyl-4-yl)-3-(4-bromo-phenyl)-N,N-dimethyl-2-propen-1-amine (BBAP), free or incorporated in preformed liposomes, on extracellular M. tuberculosis H37Rv was 8 and 25 μM (MIC), respectively. Extracellular antimycobacterial activity was not significantly improved by entrapment of BBAP in liposomes, but there was a 6.1-fold reduction of BBAP cytotoxicity on J774 macrophages. Liposomal BBAP or its free form showed IC50 values of 165 and 27 μM, resulting in a selectivity index (SI=IC50/MIC) of 3.4 and 6.6, respectively. Free BBAP in concentrations from 10 to 80 μM were quite effective in eliminating intracellular M. tuberculosis while liposomal formulation was less effective at these concentrations.

Basicities of primary arylamines and calculated amine nitrogen electronic charges

Mülliken charges on nitrogen atoms were calculated for several arylamines, utilizing the AM1 Quantum Chemistry method, relating their values to experimental amine pKa . Direct relation between pKa and nitrogen charges was found. The amines energies of protonation, calculated by the same method, also correlate directly with these charges.

Lipase and omega-transaminase catalysis in preparation of alcohol and amine enantiomers

Enantiopure intermediates are of high value in drug synthesis. Biocatalysis alone or combined with chemical synthesis provides powerful tools to access enantiopure compounds. In biocatalysis, chemo-, regio- and enantioselectivity of enzymes are combined with their inherent environmentally benign nature. Enzymes can be applied in versatile chemical reactions with non-natural substrates under synthesis conditions. Immobilization of an enzyme is a crucial part of an efficient biocatalytic synthesis method. Successful immobilization enhances the catalytic performance of an enzyme and enables its reuse in successive reactions. This thesis demonstrates the feasibility of biocatalysis in the preparation of enantiopure secondary alcohols and primary amines. Viability and synthetic usability of the studied biocatalytic methods have been addressed throughout this thesis. Candida antarctica lipase B (CAL-B) catalyzed enantioselective O-acylation of racemic secondary alcohols was successfully incorporated with in situ racemization in the dynamic kinetic resolution, affording the (R)-esters in high yields and enantiopurities. Side reactions causing decrease in yield and enantiopurity were suppressed. CAL-B was also utilized in the solvent-free kinetic resolution of racemic primary amines. This method produced the enantiomers as (R)-amides and (S)-amines under ambient conditions. An in-house sol-gel entrapment increased the reusability of CAL-B. Arthrobacter sp. omega-transaminase was entrapped in sol-gel matrices to obtain a reusable catalyst for the preparation enantiopure primary amines in an aqueous medium. The obtained heterogeneous omega-transaminase catalyst enabled the enantiomeric enrichment of the racemic amines to their (S)-enantiomers. The synthetic usability of the sol-gel catalyst was demonstrated in five successive preparative kinetic resolutions.

Changes in the biogenic amine content of the prefrontal cortex, amygdala, dorsal hippocampus, and nucleus accumbens of rats submitted to single and repeated sessions of the elevated plus-maze test

It has been demonstrated that exposure to a variety of stressful experiences enhances fearful reactions when behavior is tested in current animal models of anxiety. Until now, no study has examined the neurochemical changes during the test and retest sessions of rats submitted to the elevated plus maze (EPM). The present study uses a new approach (HPLC) by looking at the changes in dopamine and serotonin levels in the prefrontal cortex, amygdala, dorsal hippocampus, and nucleus accumbens in animals upon single or double exposure to the EPM (one-trial tolerance). The study involved two experiments: i) saline or midazolam (0.5 mg/kg) before the first trial, and ii) saline or midazolam before the second trial. For the biochemical analysis a control group injected with saline and not tested in the EPM was included. Stressful stimuli in the EPM were able to elicit one-trial tolerance to midazolam on re-exposure (61.01%). Significant decreases in serotonin contents occurred in the prefrontal cortex (38.74%), amygdala (78.96%), dorsal hippocampus (70.33%), and nucleus accumbens (73.58%) of the animals tested in the EPM (P < 0.05 in all cases in relation to controls not exposed to the EPM). A significant decrease in dopamine content was also observed in the amygdala (54.74%, P < 0.05). These changes were maintained across trials. There was no change in the turnover rates of these monoamines. We suggest that exposure to the EPM causes reduced monoaminergic neurotransmission activity in limbic structures, which appears to underlie the "one-trial tolerance" phenomenon.

Cytotoxic and DNA-topoisomerase effects of lapachol amine derivatives and interactions with DNA

The cytotoxic activity of amino (3a-e), aza-1-antraquinone (4a-e) lapachol derivatives against Ehrlich carcinoma and human K562 leukemia cells was investigated. Cell viability was determined using MTT assay, after 48 (Ehrlich) or 96 h (K562) of culture, and vincristine (for K562 leukemia) and quercetin (for Ehrlich carcinoma) were used as positive controls. The results showed dose-dependent growth-inhibiting activities and that the amino derivatives were active against the assayed cells, whereas the 4a-e derivatives were not. The allylamine derivative 3a was the most active against Ehrlich carcinoma, with IC50 = 16.94 ± 1.25 µM, and against K562 leukemia, with IC50 = 14.11 ± 1.39 µM. The analogous lawsone derivative, 5a, was also active against Ehrlich carcinoma (IC50 = 23.89 ± 2.3 µM), although the 5d and 5e derivatives showed lower activity. The interaction between 3a-d and calf thymus DNA was investigated by fluorimetric titration and the results showed a hyperchromic effect indicating binding to DNA as presented of ethidium bromide, used as positive control. The inhibitory action on DNA-topoisomerase II-a was also evaluated by a relaxation assay of supercoiled DNA plasmid, and the etoposide (200 µM) was used as positive control. Significant inhibitory activities were observed for 3a-d at 200 µM and a partial inhibitory action was observed for lapachol and methoxylapachol.

Correlation between total nitrite/nitrate concentrations and monoamine oxidase (types A and B) and semicarbazide-sensitive amine oxidase enzymatic activities in human mesenteric arteries from non-diabetic and type 2 diabetic patients

The aim of this study was to determine the correlation between total nitrite/nitrate concentrations (NOx) and the kinetic parameters of monoamine oxidase enzymes (MAO-A and MAO-B) and semicarbazide-sensitive amine oxidase (SSAO) in human mesenteric arteries. Arteries were from non-diabetic and type 2 diabetic patients with sigmoid or rectum carcinoma for whom surgery was the first option and who were not exposed to neo-adjuvant therapy. Segments of human inferior mesenteric arteries from non-diabetic (61.1 ± 8.9 years old, 7 males and 5 females, N = 12) and type 2 diabetic patients (65.8 ± 6.2 years old, 8 males and 4 females, N = 12) were used to determine NOx concentrations and the kinetic parameters of MAO-A, MAO-B and SSAO by the Griess reaction and by radiochemical assay, respectively. The NOx concentrations in arteries from diabetic patients did not differ significantly from those of the non-diabetic group (10.28 ± 4.61 vs 10.71 ± 4.32 nmol/mg protein, respectively). In the non-diabetic group, there was a positive correlation between NOx concentrations and MAO-B parameters: Km (r = 0.612, P = 0.034) and Vmax (r = 0.593, P = 0.042), and a negative correlation with the SSAO parameters: Km (r = -0.625, P = 0.029) and Vmax (r = -0.754, P = 0.005). However, in the diabetic group no correlation was found between NOx concentrations and the three kinetic parameters of the enzymes. These results suggest an important function of sympathetic nerves and vascular NOx concentrations in arteries of non-diabetic patients. Thus, these results confirm the importance of a balance between oxidants and antioxidants in the maintenance of vascular homeostasis to prevent oxidative stress.

Characterization of amine-based CO2 adsorbent for Direct Air Capture

Direct air capture technologies extract CO2 from air at a concentration of as low as 400ppm. The captured CO2 can be used for the production of synthetic methane or liquid fuels. In the literature survey of this thesis, results related to direct air capture by using solid sorbents are presented and critically discussed. In the experimental part, a proprietary amine functionalized resin is characterized for direct air capture. Structural comparison is also made to a commercial resin of similar type. Based on the literature survey, the most important parameters in direct air capture process are low adsorption and desorption temperatures, good cyclic stability in dry and humid conditions, high CO2 outlet purity and a high working capacity. Primary amine functionalized solid sorbents are found to often have good qualities for direct air capture, but overall process performance is rarely studied exhaustively. Based on FTIR spectra, both resin adsorbents are found to be consisted of polystyrene functionalized with primary amine, and capture CO2 by forming carbamate. The commercial resin is more porous, has a slightly higher particle size and contains fewer impurities. Important physical parameters are gained of the proprietary resin, such as internal porosity and median particle size. The resin’s amine group is found to endure thermal treatment reasonably well. CO2 adsorption capacity gained by thermal gravimetry from 400ppm CO2 is highest at 25oC, and is found to be reasonable compared to values presented in literature. Thus, the resin is stated to exhibit promising qualities for direct air capture.

Recueil de chants royaux, ballades et rondeaux, composés au puy de Rouen ; précédé d'un prologue adressé à Guillaume « Cretin » par « JAQUES LE LYEUR ».

Contient : 1 « Le riche don d'amoureuse mercy ». « Me NICOLE OSMONT » ; 2 « En vray amour il n'est riens impossible ». « Me JAQUES LE LYEUR » ; 3 « L'arbre de vie en l'isle fortunée ». « Me JEHAN ALYNE » ; 4 « Le sainct desert plain de manne angelique ». « Damp NICOLE LESCARRE » ; 5 « Le grant decret d'auctorité divine ». « Me JAQUES FILLASTRE » ; 6 « Le restaurant qui pour mort rend la vie ». « COURNILLE, alias TOURMENTE » ; 7 « Romme où se tient le sainct pape Innocent ». « Damp NICOLE LESCARRE » ; 8 « Le bien de paix aux humains necessaire ». « Me NICOLE DU PUYS » ; 9 « Dessus la loy d'humaine congnoissance ». « Me YSAMBERT BUSQUET » ; 10 « Femme parfaicte en nature imparfaicte ». « Me GUILLAUME THIBAULD » ; 11 « La souveraine en parfaicte beaulté ». « PIERRE CRIGNON » ; 12 « Ung corps parfaict sus ordre elementaire ». « Me JAQUES LE LYEUR » ; 13 « Au fondz d'yver printemps qui rend verdure ». « Me INNOCENT TOURMENTE » ; 14 « La purité du feu elementaire ». « Me P. AVRIL » ; 15 « La digne couche où le roy reposa ». « Me CLEMENT MAROT » ; 16 « Harnoys d'espreuve au puissant roy de gloire ». « PIERRES CRIGNON » ; 17 « Le regne franc de la loy tributaire ». « Me GUILLAUME THIBAULD » ; 18 « Saine et entiere en note et escripture ». « Me CHARLES DE SAINCT GERMAIN » ; 19 « Femme en la loy et hors la loy conceue ». « Me JO. DE BEAUVOYS » ; 20 « Selon ton nom louenge te soit faicte ». « Le general DE CAEN » ; 21 « Au grant festin du cereal convive ». « Me THOMAS LE PREVOST » ; 22 « La saincte Bible où verité repose ». « Me GUILLAUME THYBAULD » ; 23 « Pour le tout beau conceue toute belle ». « Me JEHAN DE BEAUVOYS » ; 24 « Fille obtenant la grace de son pere ». « Me ADAM LAIR » ; 25 « Le noble cueur commencement de vie ». « Me JAQUES LE LYEUR » ; 26 « Triumphanment la victoire obtenue ». « GUILLAUME DE SEVYNGUEHEN » ; 27 « Le feu d'amour pour reschauffer le monde ». « Me NICOLE DU PUYS » ; 28 « Du faulx serpent la puissance a destruicte ». « Me JAQUES LE LIEUR » ; 29 « Vray Mythridat contre mordz de vipere ». « Me INNOCENT TOURMENTE » ; 1 « Toute belle en ame et corps nect ». « Me JAQUES LE LYEUR » ; 2 « La bouge plaine de salutz ». « DUPUYS » ; 3 « La main armée aux ennemys ». « Damp NICOLE LESCARRE » ; 4 « La terre rendent bled de grace ». « Me GUILLAUME THIBAULT » ; 5 « Le nombre d'or de l'an de grace ». « Me THOMAS LEPREVOST » ; 6 « Victoire sur mes ennemys ». « Me JAQUES LELYEUR » ; 7 « Pour les siens poison importable ». « Me REUIL DOUBLET » ; 8 « Entre deux vertes une meure ». « Me THOMAS LEPREVOST » ; 9 « Entre deux vertes une meure ». « Damp NICOLE LESCARRE » ; 10 « Entre imparfaictz toute parfaicte ». « Me GUILLAUME DE SEVYNGUEHEN » ; 11 « Il n'est à Dieu rien impossible ». « Me GUILLAUME THYBAULT » ; 12 « Toutes à l'oeil, mais une au cueur ». « Me THOMAS LEPREVOST » ; 13 « Grace en toy par divin plaisir ». « Damp NICOLLE LESCARRE » ; 14 « Conception plaine de grace » ; 15 « Juste balence et loyal poix ». « Damp NICOLE LESCARRE » ; 16 « La haulte tour de fortitude ». « LESCARRE » ; 17 « La franche terre du grand roy ». « JEHAN PARMENTIER » ; 18 « D'azur à trois fleurs de lys d'or ». « PIERRE CRIGNON » ; 19 « Pour humains lyez deslier ». « Me JAQUES LE LIEUR » ; 20 « Corde l'homme et Dieu accordant ». « LIEUR » ; 21 « Ne craignez plus, la beste est prise ». « Me JAQUES LE LIEUR » ; 1 « Seule sans cy ». « Me JAQUES LE LIEUR » ; 2 « Par devolut ». « Me PIERRES AVRIL » ; 3 « Le povre Adam ». « Me NICOLE DU PUYS » ; 4 « Fors vous ». « Me NICOLE OSMONT » ; 5 « En fleur et fruict ». « Me JEHAN ALYNE » ; 6 « En unité ». « Me PIERRES AVRIL » ; 7 « Comme nature ». « Me CLEMENT MAROT » ; 8 « Grace sur grace » « Me THOMAS LEPREVOST » ; 9 « En mon concept ». « Me INNOCENT TOURMENTE » ; 10 « Ou bien de Dieu ». « GUILLAUME DE SEVYNGUEHEN » ; 11 « Une et non plus ». « Me THOMAS LEPREVOST » ; 12 « En tout honneur ». « Me PIERRES AVRIL » ; 13 « Pour moy sans plus ». « Me GUILLAUME TYBAULD » ; 14 « Grace nous vient ». « Damp NICOLE LESCARRE » ; 15 « Par mon cher filz ». « Me GUILLAUME THIBAULD » ; 16 « Mauldict serpent ». « AVRIL » ; 17 « Voulez vous myeulx ». « Me JEHAN BROYSE » ; 18 « Nonobstant loy ». « G. DE SEVYNGUEHEN » ; 19 « Au gré d'amour ». « Me GUILLAUME TYBAULD » ; 20 « Est ce bien faict ». « L'abbé DE SAINCT VANDRILLE » ; 21 « Hors paradis ». « Me JAQUES LE LYEUR » ; 1 « Deploracion de l'acteur » ; 2 « Espitre », par « LE LIEUR »