nÃo hà / Thymol (2-isopropyl-5-methyl-phenol) an isomer of Carvacrol. Present as large colorless crystals or white crystalline powder. It is a monoterpene essential oil extracted from various herbs, and the main component of the essential oil of rosemary-pepper (Lippia sidoides), constituting approximately 48% of its composition. This paper presents the behavioral actions of thymol in animal models of anxiety, depression, seizures and sedation, such as elevated plus maze (EPM), open field, rota rod, forced swim, tail suspension, seizure induced by pentylenetetrazol and pentobarbital-induced sleep time. Thymol was administered orally in male mice at doses of 25mg/kg and 50mg / kg. The results showed that thymol at both doses studied did cause muscula relaxament activits change locomotor activity on the test rota rod nor the number of crossings in the open field test, but reducedThe grooming was reduced with the administration of thymol in the open field test. At both doses studied LCE thymol increased all parameters observed suggesting a possible anxiolytic effect. Flumazenil, an antagonist of GABA / benzodiazepine, reversed this effect. In the test of sleep time induced by pentobarbital thymol not alter the latency but increased sleep duration. Although this test is sensitive to CNS depressant agents but is not specific for compounds which would interfere with the biotransformation of pentobarbital. In the test of pentylenetetrazol-induced seizures, thymol increased latency of seizure at the dose of 50mg/kg, however was not able to change the mortality of animals. Thymol showed antidepressant effect in the forced swim test and the tail suspension. This effect was reversed by pretreatment of animals with PCPA (a serotonin synthesis inhibitor), Prazosin and Yohimbine (adrenoreceptor antagonists), SCH23390 and Sulpiride (dopamine receptor antagonists). These results suggest that thymol shows anxiolytic effects probably associated with the GABAergic system and antidepressant effects associated with the serotonergic, noradrenergic and dopaminergic without causing sedation. / O Timol (2-isopropil-5-metil-fenol) um isÃmero do Carvacrol. Apresenta-se como cristal incolor grandes ou pà cristalino branco. à um monoterpeno extraÃdo do Ãleo essencial de diversas plantas aromÃticas, sendo o componente principal do Ãleo essencial do alecrim-pimenta (Lippia sidoides), constituindo aproximadamente 48% da sua composiÃÃo. Este trabalho avaliou as aÃÃes comportamentais do timol em modelos animais de ansiedade, depressÃo, convulsÃo e sedaÃÃo, tais como labirinto em cruz elevado (LCE), campo aberto, rota rod, nado forÃado, suspensÃo da cauda, convulsÃo induzida por pentilenotetrazol e tempo de sono induzido por pentobarbital. Timol foi administrado por via oral, em camundongos machos, em doses Ãnicas de 25mg/Kg ou 50 mg/Kg. Os resultados mostraram que o timol nas duas doses estudadas, nÃo causou efeito relaxante muscular no teste do rota Rod nem alterou o nÃmero de cruzamentos no teste do campo aberto, mas reduziu o grooming. No LCE ambas as doses estudadas do timol aumentaram todos os parÃmetros observados sugerindo um possÃvel efeito ansiolÃtico. O flumazenil, um antagonista dos receptores GABAA/BenzodiazepÃnico, reverteu este efeito. No teste do tempo de sono induzido por pentobarbital o timol nÃo alterou a latÃncia, mas aumentou a duraÃÃo do sono. Entretanto este teste embora sendo sensÃvel para agentes depressores do SNC nÃo à especÃfico pois compostos que possam interferir com a biotransformaÃÃo do pentobarbital. No teste da convulsÃo induzida por pentilenotetrazol, timol aumentou a latÃncia da convulsÃo na dose de 50mg/Kg, no entanto nÃo foi capaz de alterar a latÃncia de morte e a mortalidade dos animais. Timol apresentou efeito antidepressivo no teste do nado forÃado e da suspensÃo da cauda. Este efeito foi revertido pelo prÃ-tratamento dos animais com PCPA (um inibidor da sÃntese de serotonina), Prazosina e Ioimbina (antagonistas dos receptores adrenÃrgicos), SCH23390 e Sulpirida (antagonistas dos receptores dopaminÃrgicos). Estes resultados sugerem que o timol apresenta efeitos ansiolÃticos provavelmente relacionados com o sistema GABAÃrgico e efeitos antidepressivos associados aos sistemas serotonÃrgico, noradrenÃrgico e dopaminÃrgico sem causar sedaÃÃo.

Class of 2017 Abstract / Objectives: Evaluate thymoquinone (TQ) and thymol (THY) inhibitory activities against α-glucosidase enzyme by using an in vitro assay and determine the IC50 (concentration of TQ/THY to inhibit 50% of maximum enzyme activity). Methods: Various concentrations of thymoquinone and thymol were incubated, separately, with one concentration of the substrate - p-nitrophenol-α-D-glucopyranoside (PNPG) (<<Km) in presence of α-glucosidase enzyme. A positive and a negative control consisting of acarbose, and buffer, respectively, were included in the incubation as well. The incubation time was set at 30 min in a 37 °C controlled water bath. The enzyme activity was determined by detecting and quantitating the levels of p-nitrophenol using a spectrophotometer set at 405 nm. The percent inhibition exhibited by any studied drug was calculated as shown in equation 1. % inhibition = Absorbance Substrate Alone – Absorbance of Substrate + Inhibitor Absorbance Substrate Alone Results: Results of the in vitro incubation of thymoquinone, thymol and acarbose revealed “statistically” significant inhibition of -glucosidase (p<0.05). At 400 g/ml, thymoquinone inhibited the enzyme activity by ~52 % whereas the enzyme inhibition by thymol and acarbose were calculated to be ~84% and 57%, respectively. IC50 were tentatively determined although the maxima inhibitions of the inhibitors were not reached fully. IC50s were calculated as 234 μg/ml, 304 μg/ml and 157 μg/ml for each of thymoquinone, thymol and acarbose, respectively. Conclusions: Thymoquinone and thymol do exhibit antagonistic pharmacological activity against α-glucosidase.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1931. / Typescript. With this is bound: Brom derivatives of hydroxythymoquinone / By Samuel R. Chechik. Reprinted from Journal of the American Pharmaceutical Association, vol. XXII, no. 6 (June 1933), p. [506]-510. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Indiana University-Purdue University Indianapolis (IUPUI) / Purpose: This in vitro study aims to analyze the effect of combining two ADA-recommended professionally applied 1:1 Chlorhexidine/Thymol varnish ((Cervitec Plus)) and professionally prescribed 5,000 ppm fluoride toothpaste ((PreviDent 5000 Plus)) on reducing lesion depth and increasing mineral content Materials & Methods: Forty-eight dentin specimens were randomly distributed into four treatment groups (n=12 per treatment). Biofilms of Streptococcus mutans and Candida albicans were created on the polished surfaces of bovine root dentin specimens (n=12 per treatment). 1:1 Chlorhexidine/Thymol varnish was applied once then the tested 5,000 ppm fluoride toothpaste was applied for 120 seconds twice daily over the course of 2 days. Tested groups were: (1) 1:1 Chlorhexidine/Thymol varnish ((Cervitec Plus)) (C/T). (2) 5,000 ppm F toothpaste ((PreviDent 5000 Plus)) (F). (3) Combination of 1:1 Chlorhexidine/Thymol varnish ((Cervitec Plus)) & 5000 ppm F toothpaste ((PreviDent 5000 Plus)) (C/T+F). (4) Deionized water (DIW) as control group. Biofilms were analyzed for biofilm dry weight. Dentin specimens were analyzed using transversal microradiography (TMR) for mineral content change and lesion depth. PH data was analyzed using two-way ANOVA. Total biofilm dry weight data was analyzed using one-way ANOVA. Integrated mineral loss and lesion depth data was analyzed using two-way ANOVA All pair-wise comparisons from ANOVA analysis were made using Fisher’s Protected Least Significant Differences to control the overall significance level at 5%. Results: Treatment with (C/T+F) resulted in higher mean pH values compared to the control group (DIW) and (F) group. The average pH values of group (C/T) were not statistically different than group (C/T+F). the biomass of the combined S. mutans & C. albicans biofilm among all the groups were not significantly different. (DIW) presented significantly deeper lesions for both surfaces (sound &demineralized) when compared to (F) (P=0.0118), (C/T) (P=0.0002), and (C/T+F) (P<.0001). The sound surfaces for the specimens for group (C/T) and Group (F) showed superficial lesion depth. However, the sound surfaces of specimens treated with (C/T+F) showed the most superficial depth. Due to mineral gain, the demineralized surfaces of the specimens of both (C/T) & (C/T+F) showed a decrease in the lesion depth. Conclusion: Within the limitations of our study. The combination of 5,000 ppm fluoride toothpaste and CHX/Thymol had no significant effect on mineral content. However, the combination had a considerable effect on lesion depth reduction.

Campylobacter are a leading cause of bacterial derived foodborne illness. Thymol is a natural product that reduces survivability of Campylobacter in vitro. Results from animal studies, however, indicate that absorption or degradation within the stomach and small intestine may preclude delivery of thymol to the cecum and large intestine, the main sites of Campylobacter colonization. Presently, we compared the anti- Campylobacter activity of thymol against that of thymol-β-D-glucopyranoside (β-Dthymol), the latter suspected to be resistant to degradation and absorption in the proximal alimentary tract lacking β-glycosidase activity. When treated with 1 mM thymol, the survivability of Campylobacter coli and jejuni in vitro was reduced by 3.41 to 6.87 log_10 CFU mL-1 after 48-h pure culture and after co-culture, respectively. In the presence of a β-glycosidase-expressing Parabacteroides distasonis. Conversely, the survivability of C. coli and C. jejuni was reduced by 3.72 and 4.30 log_10 CFU mL-1, respectively, in cocultures treated with β-D-thymol, but not in pure cultures similarly treated. When tested in mixed cultures of porcine or bovine fecal microbes possessing endogenous β- glycosidase, C. coli and C. jejuni survivability was reduced by 3.26 and 2.50 log_10 CFU mL-1, respectively, whether treated with thymol or β-D-thymol. In mixed populations of avian crop and cecal microbes, C. jejuni survivability was reduced 1.41 to 2.32 log_10 CFU mL-1 whether treated with thymol or β-D-thymol. Thymol and β-D-thymol inhibited ammonia accumulation in mixed populations of porcine and mixed bovine fecal microbes which is consistent with free thymol’s purported role as a deaminase inhibitor. Conversely, thymol and β-D-thymol did not affect ammonia accumulation in mixed populations of avian gut microbes implicating population specific effects of these compounds. β-D-thymol, but not thymol, reduced accumulation of fermentation acids indicating the conjugate inhibited fermentation which may limit its application to the last meal or last few meals before harvest. Oral administration of 150 μmol β-D-thymol reduced C. jejuni in avian crop, but not in cecal contents; treatment with thymol was ineffective. These results indicate that β-D-thymol, or similar β-glycosides, may be a suitable candidate to escape absorption and degradation within the proximal alimentary and retain its anti-Campylobacter properties. Further research is needed to reduce such technology to practice.

This thesis is regarded with the biomimetic total synthesis of phenolic natural products and describes two different projects. Chapter 1 introduces phenolic natural products, the most important biosynthetic pathways for their formation and some examples of relevant biomimetic syntheses. A short introduction to dimeric and pseudo-dimeric natural products can also be found in this chapter. Specific introductions can be found at the start of Chapters 2 and 3. Chapter 2 describes the total synthesis of a dimeric thymol derivative isolated from Arnica sachalinensis (which we have named “thymarnicol”). Inspired by the biosynthesis proposed by Passreiter and co-workers, we tested and confirmed the feasibility of a key hetero-Diels–Alder dimerisation step. During our investigations, we gained significant new insights into the origin and reactivity of thymarnicol. The final oxidative cyclisation has been found to occur spontaneously upon exposure to visible light in air. Chapter 3 discusses our efforts to develop a divergent biomimetic synthetic strategy towards a family of prenylated phenylpropanoid natural products isolated from Illicium genus plants. Our first biomimetic approach revealed the chemical instability of our proposed key intermediates. Therefore, a revised approach was trialled, allowing the total synthesis of a small set of natural products and related structures. We envisage that this strategy could be exploited by accessing a large number of members of this family of compounds.

Submitted by Haroudo Xavier Filho (haroudo.xavierfo@ufpe.br) on 2016-04-14T18:46:13Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação Tacilene Luzia Silva.pdf: 1235794 bytes, checksum: f6e18d8a1d865ebf8536ae8b8a1666f3 (MD5) / Made available in DSpace on 2016-04-14T18:46:13Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação Tacilene Luzia Silva.pdf: 1235794 bytes, checksum: f6e18d8a1d865ebf8536ae8b8a1666f3 (MD5) Previous issue date: 2015-02-13 / CNPq / Pseudomonas aeruginosa é uma bactéria Gram negativa, oportunista e ubíqua, frequentemente associada a infecções graves em pacientes imunocomprometidos. Em razão do aumento de resistência dessa bactéria aos múltiplos antimicrobianos, surgem à preocupação e a procura por novas alternativas terapêuticas, com as substâncias bioativas de origem natural representando uma importante fonte para obtenção desses medicamentos. O objetivo do presente estudo foi determinar a atividade sinérgica do timol e agentes antimicrobianos frente a cepas de Pseudomonas aeruginosa multirresistentes e avaliar os efeitos dessa interação sobre a biossíntese de biofilme e de piocianina. Para isso, numa primeira etapa foi determinada a concentração inibitória e bactericida mínima do timol e de antimicrobianos (Polimixina B, ceftazidima, piperacilina/tazobactam, cefepima, ciprofloxacino e meropenem) frente a dez cepas de Pseudomonas aeruginosa. O estudo da interação entre o timol e os agentes antimicrobianos foi realizado pelo método do tabuleiro de xadrez. Os critérios utilizados para avaliar a atividade sinérgica foram definidos pelo Índice da Concentração Inibitória Fracionada (FIC índex). A partir dos melhores valores do FIC índex das associações timol/antimicrobiano foram avaliadas a atividade sobre a produção de biofilme e piocianina. Três cepas (LFBM 01, LFBM 02, LFBM 16) apresentaram um perfil de resistência ao meropenem e cefepima e um efeito sinérgico foi observado entre o timol e meropenem ou cefepima sobre essas cepas. A associação timol/cefepima inibiu a biossíntese do biofilme em até 99,76%, e a associação timol/meropenem mostrou ser mais eficaz na inibição da piocianina cujos valores foram de até 84,33%. O timol associado ao meropenem ou cefepima, age sinergicamente, inibindo cepas de Pseudomonas aeruginosa multirresistentes e interferindo na biossíntese de biofilme e piocianina. / Pseudomonas aeruginosa is a Gram negative bacteria, opportunistic and ubiquitous, often associated with severe infections in immunocompromised patients. Due to the increased resistance of the bacteria to multiple antibiotics, there are the concerns and the search for new therapeutic alternatives, with the bioactive substances of natural origin represents an important source for obtaining these drugs. The aim of this study was to determine the synergistic activity of thymol and antimicrobials agents multiresistant Pseudomonas aeruginosa strains and evaluate the effects of this interaction on the biofilm biosynthesis and pyocyanin. For this, a first step was determined and the minimum inhibitory concentration of thymol and bactericidal antibiotics (polymyxin B, ceftazidime, piperacillin / tazobactam, cefepime, ciprofloxacin and meropenem) compared to ten strains of Pseudomonas aeruginosa. The study of the interaction between the thymol and antimicrobial agents was carried out by the checkerboard method. The criteria used to evaluate the synergistic activity were defined by the Index of Fractional Inhibitory Concentration (FIC index). From the best FIC index values of associations thymol / antimicrobial activity were evaluated on the production of biofilm and pyocyanin. Three strains (LFBM 01, LFBM 02, LFBM 16) showed an meropenem resistance profile and cefepime and a synergistic effect was observed between the thymol and meropenem or cefepime on these strains. The thymol / cefepime combination inhibited biofilm biosynthesis up to 99.76%, and thymol association / meropenem was more effective in inhibiting pyocyanin with values of up to 84.33%. The thymol associated with meropenem or cefepime, acts synergistically by inhibiting multidrug-resistant Pseudomonas aeruginosa strains and interfering in the biosynthesis of biofilm and pyocyanin.

L'objectif de ces travaux était de mettre au point des vecteurs de diffusion efficaces du thymol pour lutter contre un acarien parasite des abeilles. Le choix s'est porté sur la formation de nano-objets par émulsification spontanée pouvant libérer efficacement du thymol grâce à leur grande surface spécifique. L'émulsification spontanée par « effet Ouzo » a été choisie en raison de (i) la simplicité du procédé nécessaire pour son application par les apiculteurs et de (ii) la possibilité de former une grande diversité de nano-objets. L'émulsification spontanée par effet Ouzo a tout d'abord été étudiée fondamentalement avec un polymère (nanoprécipitation), le polyméthacrylate de méthyle (PMMA), pour s'affranchir des phénomènes déstabilisants typiques des émulsions tels que le mûrissement d'Ostwald et la coalescence. Cette étude a permis de définir clairement les compositions du système PMMA/solvant/eau pour lesquelles la nanoprécipitation du PMMA induit la formation exclusive de nanoparticules de distribution de taille étroite (zone Ouzo) ou la formation de nanoparticules additionnées de macroparticules (zone non-Ouzo), séparées par la limite Ouzo. Deux mécanismes de formation des nanoparticules ont été déduits suivant la sursaturation du PMMA (nucléation et croissance ou nucléation et agrégation). L'influence des stabilisants a montré l'importance de l'adsorption des ions OH- sur la taille des nanoparticules et sur le déplacement de la limite Ouzo alors que seule la stabilité colloïdale est améliorée avec l'ajout de tensioactifs. Cette étude fondamentale a servi de base pour la formation des nanogouttelettes de thymol et des nanocapsules thymol-PVA réticulé et thymol-PMMA par effet Ouzo. Des nanoparticules thymol-PVP ont également été formées par complexation de la poly(N-vinyl-2-pyrrolidone) en milieu aqueux. Ces nano-objets de thymol ont été testés sur des ruches infestées pour déterminer leur efficacité d'éradication de l'acarien Varroa Destructor. / The objective of this work dealt with setting up efficient thymol diffusion vectors to fight against a bee mite, the Varroa Destructor. The formation of nano-objects by spontaneous emulsification was investigated because they provide large specific area to enhance thymol evaporation. Spontaneous emulsification by so-called Ouzo effect was chosen because of (i) the simplicity of the process necessary for the transfer to beekeepers and (ii) the great diversity of nano-objects morphologies which can be designed. Spontaneous emulsification by Ouzo effect was first studied fundamentally with a polymer (nanoprecipitation), the poly(methyl methacrylate) (PMMA), in order to avoid typical emulsion destabilizing phenomena such as Ostwald ripening and coalescence. This study enabled to clearly define the PMMA/solvent/water system compositions for which PMMA nanoprecipitation induces only formation of nanoparticles with a narrow size distribution (Ouzo domain) or formation of microparticles besides nanoparticles (non-Ouzo domain), separated by the Ouzo boundary. Two nanoparticles formation mechanisms were deduced with respect to the supersaturation of PMMA (nucleation and growth or nucleation and aggregation). Stabilizers influence set off the importance of OH- ions adsorption on nanoparticles size and on Ouzo boundary shifting whereas only colloidal stability is improved through surfactant addition. This fundamental study laid down basis for thymol nanodroplets and for thymol-cross linked PVA and thymol-PMMA nanocapsules formation by Ouzo effect. Thymol-PVP nanoparticles were also prepared by poly(N-vinyl-2-pyrrolidone) complexation in aqueous medium. These thymol nano-objects were tested on infested beehives to determine their efficiency to eradicate the Varroa Destructor mite.

Plante présente dans de nombreux pays méditerranéens, l'Origan (genre Origanum) a été classé par Ietswaart en 74 espèces, sous-espèces, variétés ou hybrides. La composition chimique des huiles essentielles (HE) d'une trentaine d'espèces a été étudiée dans ce travail. Le matériel végétal a été fourni par le CNPMAI de Milly-la-Forêt qui a réalisé des cultures à partir de semis de graines collectées dans les pays d'origine. Les plants ainsi obtenus ont été récoltés, séchés, et les HE ont été extraites par hydrodistillation selon le procédé décrit par la Pharmacopée Européenne 5ème éd. L'analyse des 457 échantillons d'HE a été effectuée au moyen des techniques de CPG, soit couplée à la spectrométrie de masse pour l'identification des composés, soit couplée à un détecteur à ionisation de flamme pour leur quantification. L'analyse des résultats montre que les phénols sont présents dans la quasi-totalité des espèces étudiées, le carvacrol est le plus représenté puisque les HE de 22 espèces en renferment plus de 40 %, tandis que le thymol atteint des teneurs de plus de 40 % dans les HE de 8 espèces. Les monoterpènes oxygénés sont présents à plus de 50 % dans 7 espèces, les plus importants étant le linalol, l'α-terpinéol, le trans-hydrate de sabinène et le terpinène- 4-ol. Une seule espèce fournit une HE renfermant une quantité importante d'hydrocarbures monoterpéniques. Ce travail a permis d'une part d'indiquer des compositions d'HE non encore étudiées à ce jour et d'autre part de mettre en évidence des spécificités intra et inter espèces. En effet, lorsque le nombre d'échantillons d'HE analysés était suffisant, une étude statistique par ACP et test de Student a permis de montrer la présence de plusieurs chémotypes au sein d'une même espèce. L'origine géographique serait une variable importante puisque les HE de certaines espèces natives d'isolats géographiques (Ile de Chypre) possèdent généralement une composition unique contrairement à celles originaires du continent où la présence de 2 ou 3 chémotypes a parfois été montrée. Ce travail a aussi permis d'établir que O. dubium et O. majorana var. tenuifolium, initialement confondus, sont en fait 2 espèces botaniquement distinctes. La composition de leurs HE confirme cette différenciation : la première présente 2 chémotypes (1 à thymol et 1 à carvacrol), alors que l'HE de la seconde se compose principalement d'α-terpinéol, de trans-hydrate de sabinène et de terpinène-4-ol. Il n'a par contre pas été possible d'établir de manière formelle une relation chimiotaxonomique entre la composition chimique des HE d'Origan et la classification proposée par Ietswaart.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.