No description available.

Parabens are the esters of p-hydroxybenzoic acid and are commonly used as preservatives in personal care products, pharmaceutical preparations and cosmetics. Recently parabens have been found to be estrogenic, bringing into question if exposure to them is adversely affecting human health. Given exposure to multiple xenoestrogens is constant; research has been carried out to determine what effect combinations of xenoestrogens might have on human and environmental health. Parabens are almost always present in combinations in formulae as this increases their antimicrobial activity, so it is important to know what the effect of this is. The main aim of this study was to determine what the effect of combining methylparaben and butylparaben together has on the proliferation of MCF-7 breast cancer cells, which proliferate in the presence of estrogen. This study was carried out by exposing MCF-7 breast cancer cells to combinations of methylparaben and butylparaben and measuring cell proliferation by counting cells using a cytometer. The results show that butylparaben caused a greater increase in cell proliferation compared to methylparaben. When methylparaben and butylparaben were combined together, the resulting cell proliferation was greater than the cell proliferation produced by either methylparaben or butylparaben alone at a concentration twice the amount of either paraben concentration contained within the mixture. These results were analysed using Analysis of Variance, which determined the combination treatments were statistically different from the single treatments according to Fishers method. This suggests that there is a synergistic effect produced when methylparaben and butylparaben are combined together, however large variation and dose dependent discrepancies means this result is uncertain and further studies need to be carried out.

No / A microemulsion electrokinetic chromatography (MEEKC) method has been developed and validated for the determination of 4-hydroxybenzoates and their impurities. These materials are commonly known as parabens and are widely used as preservatives in foods, cosmetics and pharmaceuticals. The method was shown to be selective and quantitative for the methyl, ethyl, propyl and butyl esters of 4-hydroxybenzoic acid. An internal standard, 4-hydroxyacetophenone, was employed to improve injection precision and detector linearity. In addition, 4-hydroxybenzoic acid, the major degradent, could also be monitored at the 0.1% (m/m) level. The method was successfully validated for assay and detection of the impurities in 4-hydroxybenzoic acid methyl ester and 4-hydroxybenzoic acid propyl ester samples and for the determination of 4-hydroxybenzoic acid methyl ester in a liquid pharmaceutical formulation. The determination of paraben content by MEEKC in a liquid sample was consistent with HPLC analysis. This work is the first reported validated MEEKC method and shows that the methodology can be successfully implemented into routine quality control testing.

Parabens have been used as antimicrobial preservatives in multiple different types of products for decades, however relatively recent studies have caused concern as to whether their wide-use could be potentially harmful. The following paper reviews the extensive areas of human exposure, from mother to fetus, infants via breast milk, baby and child care products through adult personal care products, and other environmental sources. The potential impacts on human health are also discussed. Parabens predominantly impact biological systems as an endocrine disruptor not only by binding to the human Estrogen Receptor directly, but increasing the availability of naturally occurring 17β-estradiol, further potentiating the effect. Alternative antimicrobial preservatives are also discussed, along with their efficacies and potential health concerns. Common alternatives found in personal care products include phenoxyethanol, methylisothiazolinone, and formaldehyde releasers. Additionally, weak organic acids and plant-derived essential oils are also used in personal care products, but tend to be added more so to food products to prevent the growth of spoilage bacteria, fungi and mold. The potential for these alternatives to replace the use of parabens in personal care products, our greatest area of exposure, is very promising. If parabens in personal care products were replaced with a safe and effective alternative, then the other areas of environmental exposure would likely be negligible to produce any harm on society. Future investigation into the nuances of the various plant-derived essential oils and effective formulations for preservation, is likely the most promising solution, due to their mostly harmless nature. Lastly, the discussion of proposed future research in order to lead to a more definitive connection between paraben exposure and adverse health effects is presented.

No description available.

Le triclosan (TCS), le triclocarban (TCC) et les parabènes (esters de l'acide para-hydroxbenzoïque) sont employés en tant qu'antiseptiques et agents conservateurs dans les produits de soins corporels. Leur usage génère des inquiétudes sur leur devenir et leur effet potentiel sur la faune et la flore (Bazin et al., 2010). En effet, ils sont introduits dans le milieu récepteur principalement via les effluents des stations d'épuration et les rejets urbains de temps de pluie (McAvoy et al., 2002; Agüera et al., 2003). Les principaux objectifs de ces travaux étaient de mettre en place une base de données sur les niveaux d'imprégnation dans les eaux résiduaires urbaines de deux agglomérations, Paris et Beyrouth par temps sec, et d'évaluer l'efficacité des traitements présents dans différentes stations d'épuration : deux à Paris une à Beyrouth. Le suivi de la contamination des émissaires pour les agglomérations de Paris et Beyrouth a permis plusieurs avancées sur les connaissances relatives à la fois à l'analyse des parabènes, triclosan et triclocarban mais aussi à la contamination des eaux résiduaires urbaines dans les deux pays par ces molécules. Ainsi sur les aspects analytiques, une très grande stabilité des parabènes, triclosan et triclocarban, une fois fixés sur cartouche Oasis® HLB, après extraction sur des échantillons d'eaux usées préalablement acidifiés, a été mise en évidence. Un test de conservation, mené sur une période de 4 mois, a montré la possibilité de conduire des analyses des parabènes, triclosan et triclocarban dans des pays ne possédant pas la chaîne analytique complète (absence d'un appareil de type UPLC/MSMS, par exemple), ce qui ouvre des perspectives intéressantes pour des pays émergents. Pour les niveaux de contamination rencontrés, nos résultats montrent que les méthylparabène, éthylparabène et propylparabène présentent les concentrations les plus élevées alors que le benzylparabène n'a jamais été observé dans aucun échantillon. Les parabènes sont présents en phase dissoute à plus de 99 %. Les log(Kd) estimés pour ces composés sont compris entre 0,8 et 2 (en valeur médiane) pour la France et 1,3 et 2,3 pour le Liban. Les MES ne sont donc pas le principal vecteur de ces composés dans les émissaires. Le triclosan est lui majoritairement présent en phase particulaire, il offre des log(Kd) plus élevés que ceux des parabènes, voisins de 4 pour les deux pays. Le triclocarban est plus singulier. Dans les émissaires de l'agglomération parisienne, son log(Kd) est plus faible que celui du triclosan (3,4 contre 4) alors que c'est une situation inverse qui est obtenue Beyrouth : 4,6 pour le triclocarban et 4,1 pour le triclosan, conséquence directe de la plus forte contribution de la phase particulaire à la charge totale en triclocarban au Liban. Sur la base des concentrations mesurées, pour la première fois en France, des flux annuels par équivalent habitant ont pu être déterminés pour l'ensemble des composés ; ils sont de 1158 mg/EH/an pour MeP, 276 mg/EH/an pour EtP, 253 mg/EH/an pour PrP, 12 mg/EH/an pour IsoBuP, de 66 mg/EH/an pour BuP, 268 mg/EH/an pour TCS et 9 mg/EH/an pour TCC. Ces estimations n'ont pu être réalisées pour le Liban car les mesures de débits n'étaient pas possibles sur les sites suivis. Bien que les phénomènes mis en jeu diffèrent suivant les composés, il a été montré que les deux stations d'épuration de Seine Centre et Seine Amont éliminent à plus de 97 % les parabènes, le triclosan et le triclocarban / Triclosan (TCS), triclocarban (TCC) and parabens (esters of para-hydroxbenzoic acid) are used as antiseptics and preservatives in pharmaceuticals personal care products. Their use generates concerns on their fate and their potential effect on the fauna and flora (Bazin et al., 2010). Indeed, they are introduced in the receiving waters primarily via effluents from wastewater treatment plants and combine sewer overflows (McAvoy et al., 2002; Agüera et al., 2003). The main objectives of this work were to set up a database on levels of impregnation in the urban wastewater from two cities, Paris and Beirut by dry weather, and to assess the effectiveness of treatments in different wastewater treatment plants: two in Paris one in Beirut. Monitoring of the contamination of the main tributaries of Paris and Beirut has allowed more advanced knowledge of both the analysis of parabens, triclosan and triclocarban but also to urban waste water contamination in both countries by these molecules. Thus on analytical aspects, a very high stability of parabens, triclosan and triclocarban, once fixed on cartridge OASIS HLB, after extraction on previously acidified samples of wastewater, has been highlighted. A test of conservation, carried out over a period of 4 months, showed the possibility of conducting analyses of parabens, triclosan and triclocarban in countries without any analytical devices (UPLC/MSMS, for example), which opens up interesting prospects for emerging countries. With respect to levels of contamination, our results showed that methylparaben, propylparaben and ethylparaben have the highest concentrations while benzylparaben has never been observed in any sample. Parabens were present in the dissolved phase at more than 99 %. The log(Kd) estimated for these compounds were between 0.8 and 2 (median values) for France and 1.3 and 2.3 for Lebanon. TSS were not the main conveyor of these compounds in the tributaries. Triclosan was predominantly present in the particulate phase, it presented log(Kd) higher than parabens, of about 4 for the two countries. Triclocarban was more singular. For the emissaries in the Paris region, its log(Kd) was lower than that of triclosan (3.4 against 4) whereas a reverse situation was observed in Beirut: 4.6 for triclocarban and 4 1 for triclosan. This was a direct consequence of the higher contribution of the particulate phase to the total load of triclocarban in Lebanon.Based on measured concentrations for the first time in France, the yearly flows per inhabitant equivalent have been determined for all the compounds, they were of 1158 mg for MeP, 276 mg for EtP, 253 mg for PrP, 12 mg for IsoBuP, 66 mg for BuP, 268 mg for TCS and 9 mg for TCC. These estimates have not been made possible for Lebanon because flow measurements were not available on the monitored sites. Although the phenomena involved differ depending on the compounds, it has been shown that the two wastewater treatment plants of Seine Centre and Seine Aval removed at more than 97 % parabens, triclosan and triclocarban

Este trabalho descreve o desenvolvimento de novos métodos cromatográficos em conjunto com técnicas de microextração para determinação de parabenos em produtos cosméticos e leite humano e rifampicina em amostras de plasma. Destaca-se também o desenvolvimento da fase extratora molecularmente impressa para extração em fase sólida (SPE) de parabenos em amostras de leite humano. O capítulo I descreve a avaliação da extração sortiva em barra de agitação (SBSE) em conjunto com a cromatografia líquida (LC) com detecção espectrofotométrica (LC-UV) para análises de parabenos em produtos cosméticos para fins de controle de qualidade. As variáveis do processo de extração SBSE, tais como tempo e temperatura de extração, pH e força iônica da amostra e condições de dessorção foram otimizadas para aumentar a sensibilidade analítica do método e diminuir o tempo de análise. O método SBSE/LC-UV desenvolvido apresentou faixa linear correspondente ao limite de quantificação (LQ) a 2,50 µg. mg-1 e coeficientes de determinação maiores que 0,993. Os valores de coeficiente de variação resultantes das análises de precisão interensaios foram 5,0% para todos os parabenos analisados e a exatidão variou de 90 a 100%. O método desenvolvido foi aplicado para análises de amostras de produtos cosméticos comerciais (cremes hidratantes, antitranspirantes em creme e filtros solares). O método SBSE/LC-UV padronizado e validado resultou nas seguintes vantagens em relação aos métodos convencionais: simplicidade no preparo de amostra, redução do volume de solvente orgânico e da quantidade de amostra utilizada. O capítulo II descreve o desenvolvimento da fase extratora molecularmente impressa para SPE de parabenos em amostras de leite humano e análises por cromatografia em fase líquida com detecção espectrofotométrica (SPE/LC-UV). Os polímeros de impressão molecular, materiais sintéticos baseados em sistemas biomiméticos, foram sintetizados através do processo sol-gel tendo como molde, o benzilparabeno. Após a remoção do molde, cavidades seletivas (sítios de reconhecimento molecular) ao benzilparabeno e análogos estruturais foram reveladas. O método SPE/LC desenvolvido apresentou faixa linear correspondente ao limite de quantificação a 150 ng. mL-1 e coeficientes de determinação 0,992. Os valores de coeficiente de variação resultantes das análises de precisão interensaios foram 13% e a exatidão variou de 86 a 117%. A aplicabilidade do método SPE/LC foi demonstrada através das análises de amostras de leite humano de lactantes. Segundo os parâmetros de validação analítica avaliados, o método padronizado SPE/LC-UV é adequado para análises de parabenos em amostras de leite humano. O capítulo III descreve a avaliação da microextraçao em fase sólida no capilar (in-tube SPME) acoplada à cromatografia líquida (LC) com detecção espectrofotométrica (LC-UV) para análises de rifampicina em amostras de plasma para fins de monitorização terapêutica. As variáveis in-tube SPME, tais como fase estacionária da coluna capilar, volume de amostra, ciclos aspirar/dispensar e vazão foram otimizadas visando obter maior eficiência do processo. O método in-tube SPME/LC desenvolvido apresentou faixa linear correspondente ao limite de quantificação (0,1 µg. mL-1) a 100 µg. mL-1 e coeficientes de determinação igual a 0,998. Os valores de coeficiente de variação resultantes das análises de precisão interensaios foram 2% e a exatidão variou de 83 a 92%. A aplicabilidade do método in-tube SPME/LC, padronizado e validado foi comprovada através das análises de amostras de plasma de pacientes em tratamento com rifampicina. O método in-tube SPME/LC resultou na automação do processo de análise, maior precisão analítica, menor tempo de análise, menor volume de solvente orgânico e de fluido biológico. / This work describes the development of chromatographic methods in combination with microextraction techniques for the determination of parabens in cosmetic and human milk samples and of rifampicin in plasma samples. The design of a molecularly imprinted extraction phase for the solid-phase extraction (SPE) analysis of parabens in human milk samples is also reported. Chapter I describes the evaluation of the stir bar sorptive extraction (SBSE) in combination with liquid chromatography (LC) with UV detection (LC-UV) for the analysis of parabens in cosmetics aiming at quality control. The SBSE variables such as extraction time, temperature, pH of the matrix, ionic strength, and desorption conditions have been optimized, in order to establish the parabens partition equilibrium in a short analysis time. The linear range of the SBSE/LC method lay from LOQ to 2.5 µg. mg-1, with a coefficient of determination higher than 0.993. The interday precision of the SBSE/LC method presented a coefficient of variation lower than 5%, and the accuracy ranged from 90 to 99%. The effectiveness of the proposed method for the analysis of commercial cosmetic products such as body creams, antiperspirant creams, and sunscreens has been proven. Therefore, the combination of SBSE with liquid desorption, followed by LC analysis, provides a simple, and selective tool for the analysis of parabens in cosmetic products using minimized volume of organic solvent as well as very small amount of the target sample. Chapter II presents the development of a molecularly imprinted extraction phase for the SPE analysis of parabens in human milk samples. The molecularly imprinted polymers, which are synthetic materials based on biomimetic systems, were synthesized by the sol-gel technology in the presence of the template (benzilparaben). After template removal, selective cavities (benzilparaben) were revealed for parabens selective extraction. The linear range of the SPE/LC method lay from LOQ to 150 ng. mL-1, with a coefficient of determination higher than 0.992. The interday precision of the SPE/LC method presented a coefficient of variation lower than 13%, and the accuracy ranged from 86 to 117%. The effectiveness of the proposed method for the analysis of human milk samples has been demonstrated. According to the evaluated analytical validation parameters, the SPE/LC-UV method is suitable for the analysis of parabens in human milk samples. Chapter III depicts the evaluation of solid-phase microextraction in the capillary (in-tube SPME) in combination with liquid chromatography (LC) with UV detection (LC-UV) for the analysis of rifampicin in plasma samples for therapeutic drug monitoring. The in-tube SPME/LC method was linear over the LOQ (0.1) to 100 g. mL-1 range, with a linear coefficient value (r2) of 0.998. The inter-assay precision presented coefficient of variation 2%, and the accuracy ranged from 83 to 92%. The effectiveness and practicability of the proposed method have been by analysis of plasma samples from ageing patients undergoing therapy with rifampicin. The in-tube SPME/LC method allowed for automated continuous sample preparation (extraction, concentration, desorption, and injection of analytes) and minimized the analysis time as well as the volumes of organic solvent and biological fluid.

Bisfenóis, filtros UV de benzofenona, parabenos e antimicrobianos como triclocarban são amplamente utilizados em produtos alimentares, farmacêuticos, cosméticos e de cuidados pessoais e também são encontrados como contaminantes. A maioria destes compostos apresentam possíveis efeitos adversos à saúde, principalmente devido ao fato de sua potencial atividade desreguladora endócrina. Neste sentido, é crescente o interesse pelo desenvolvimento de métodos analíticos que sejam mais simples e que possam ter a capacidade de detecção do maior número de analitos possíveis simultaneamente para uso em estudos de biomonitoramento humano. O objetivo deste projeto foi desenvolver um novo método de preparo de amostras em microextração em sorvente empacotado (MEPS, do inglês \"microextraction by packed sorbent\") para a extração simultânea de substâncias potencialmente desreguladoras endócrinas (parabenos, bisfenóis, benzofenonas e triclocarban). Em 250 ?L de urina sintética (pH 5,3) foram adicionados os analitos a uma concentração de 20 ng/mL e diluídos com 250 ?L de água. Após este procedimento, os compostos foram extraídos manualmente da amostra de urina usando MEPS C18 com 5 ciclos de aspirar-dispensar de 100 ?L. A eluição dos analitos foi realizada utilizando 100 ?L (metanol/água 80:20), seguido de análise em LC-MS/MS. O cartucho MEPS, após a limpeza, foi reutilizado para extrações múltiplas sem a presença de efeito de memória. As separações cromatográficas foram conduzidas em uma coluna C18 a 40 °C. A fase móvel foi composta por um gradiente de metanol e água a uma vazão de 500 ?L/min. Os dados foram adquiridos no modo MRM com íons negativos como precursores. O método MEPS-LC-MS/MS proposto apresentou curva de calibração linear para todos os analitos com coeficiente de correlação (r) maior que 0,99 no intervalo do limite inferior de quantificação (LIQ) a 20,0 ng/mL. Os LODs variaram de 0,005-0,1 ng/mL e os LIQ variaram de 0,5-2,5 ng/mL. Além disso, a precisão foi expressa como o coeficiente de variação, onde os valores obtidos foram menores que 20% (n=3) nos LIQ e menores que 15% (n=3) nas concentrações de 10,0 e 20,0 ng/mL. A exatidão foi expressa na forma de erro padrão relativo, onde os valores obtidos não foram superiores a ±20% (n=3) para os LIQ e ±15% (n=3) nas concentrações 10,0 e 20,0 ng/mL. O procedimento MEPS proposto apresentou vantagens que incluem a possibilidade de extração e determinação simultânea de 16 analitos em urina, com redução dos volumes de amostra e solvente utilizados, além de vantagens como tempo reduzido de preparo de amostra, clean up da matriz e dispensa etapa prévia ao preparo de amostra / Bisphenol, benzophenone UV filters, parabens and antimicrobials as triclocarban are widely used in food, pharmaceuticals products, cosmetic and personal care products or they are fond as contaminants. Most of these compounds show possible health adverse effects, mainly due to the fact of its potential endocrine disrupting activity. Thus, there is an increasing interesting in new analytical method development that will be simple and able to detect largest number of analytes possible simultaneously to be used in human biomonitoring studies. The project goal was developed a new sample preparation methody in Microextraction in packed sorbent (MEPS) to simultaneous extraction followed by liquid chromatography coupled to mass spectrometry in tandem analysis (LC-MS/MS) of 16 substances potentially endocrine disrupting (parabens, bisphenols, benzophenones and triclocarban). In 250 ?L of synthetic urine (pH 5.3) were spiked with compounds at a concentration of 20 ng/mL and diluted with 250 ?L of water. After this procedure, the compounds were extracted manually from urine sample using MEPS C18 with 5 draw-eject 100 ?L cycles. The elution was performed using 100 ?L (methanol/water 80:20) followed by LC-MS/MS analysis. The MEPS cartridge, after cleaned, was used for multiple extractions without any carry-over effect. Chromatographic separations were carried out on a C18 column at 40 oC. The Mobile phase was composed by a gradient methanol and water at a flow rate of 500 ?L/min. Data were acquired the MRM mode with negative ions as precursors. The proposed MEPS-LC-MS/MS method showed calibration curve linear to all analytes with correlation coefficient higher than 0,99 in the range from low limit of quantification (LIQ) to 20,0 ng/mL. The LODs range from 0,005-0,1 ng/mL and LIQ range from 0,5 to 2,5 ng/mL. Moreover, the precision was reported as variation coefficient, where the values were less than 20% (n=3) to the LIQ and less than 15% (n=3) to 10,0 and 20,0 ng/mL concentrations. The accuracy was reported as relative standard error, where the values were less than ±20% to the LIQ and less than ±15% (n=3) to 10,0 and 20,0 ng/mL concentrations. The MEPS procedure proposed showed advantages including possibility to extraction and simultaneous determination of 16 analytes in urine, with sample and solvents volume reduction besides it shows advantages as time reducing in sample preparation, matrix clean up and dispense previous sample preparation step.

Les cucurbitacines et les parabènes sont des substances d'origine naturelle appartenant à la famille des triterpéniques cycliques et des esters de l'acide-hydroxybenzoïque, respectivement. Ils sont connus pour posséder chez l'homme plusieurs effets pharmacologiques potentiellement intéressants. Le but de ce travail est d'étudier la biotransformation d'une série de trois cucurbitacines et de cinq parabènes dans le foie humain in vitro, essentiellement par glucuronoconjugaison et hydrolyse et caractériser l'effet cytotoxique des cucurbitacines sur une lignée cellulaire du chondrosarcome humain SW 1353. Les résultats ont montré que les cucurbitacines I et D sont plus cytotoxiques que la cytochalasine D vis-à-vis SW 1353 et entraînent l'apoptose des cellules après 12h de traitement à 1 µM alors que la cucurbitacine E présente une cytotoxicité à 10 µM. L'étude in vitro de biotransformation chez l'homme montre que les cucurbitacines sont surtout sulfo- et glucuronoconjuguées (méthodes radiochimiques) par les isoformes de la famille 1A essentiellement. La cucurbitacine E est également activement hydrolysées (Km 22 µM et Vmax 571 nmol/mg /min) en cucurbitacine I dans le foie humain. Par contre, ces substances sont très faiblement hydroxylées. Les acides oléanolique, ursolique et l'érythrodiol, de structure apparentée aux cucurbitacines, sont aussi glucuronoconjuguées au même taux dans les microsomes hépatiques humains mais avec des affinités 100 fois plus élevées. Les parabènes sont rapidement hydrolysés par des estérases dans les microsomes hépatiques humains en acide 4-hydroxybenzoïque, et leur hydrolyse diminue avec la longueur de la chaîne alkyle. Les parabènes, l'acide caféique, le tyrosol et l'hydroxytyrosol, de structure apparentée aux parabènes, sont activement glucuronoconjuguées par les UGTs des familles 1A et 2B. Cependant, l?acide 4-hydroxybenzoïque n'est pas un bon substrat pour les UGTs / Cucurbitacins and parabens are natural compounds belonging to cyclic triterpenoid and alkyl ester of 4-hydroxybenzoic acid, respectively. They are known for their potential valuable pharmacological effects. The aim of this work was to study the biotransformation of a series of three cucurbitacins and six parabens in human liver, in vitro, essentially by glucuronidation and hydrolysis reactions, and by comparision with other natural substances structurally related, and to characterize the cytotoxicity effect of cucurbitacins on a human chondrosarcoma cell line, SW 1353. The results showed that cucurbitacins I and D showed more cytotoxicity than cytochalasin D and led to cell apoptosis after 12h of treatment at 1 ?M. Cucurbitacin E showed its cytotoxic effect at 10 µM. The in vitro study of cucurbitacins biotransformation in man showed that these substances are sulfated, glucuronidated (radiochemical methods). Moreover, cucurbitacin E was actively hydrolyzed (Km 22 µM and Vmax 571 nmol/mg protein/min) leading to cucurbitacin I in man liver. On the other hand, they are weakly hydroxylated. Oleanolic acid, ursolic acid and erythrodiol, chemically related to cucurbitacins, were glucuronidated at the same rate in human liver microsomes, however, with affinities 100 times greater. Parabens were quickly hydrolyzed in human liver microsomes by esterases and hydrolysis decreased with side chain length. Parabens, caffeic acid, tyrosol and hydroxytyrosol were actively glucuronidated by the UGTs of both families 1A and 2B. However, p-hydroxybenzoic acid is not a good substrate for UGTs

Mechanosensitive (MS) channels are a class of ion channels which are gated by membrane stretch. The mechanosensitive channel of large conductance (MscL) of the bacterium E.coli has become a prototype MS channel for studying structure-function relationships in this class of ion channels. MscL homologues have commonly been found in Gram-negative and Gram-positive bacterial strains forming a sub-family of a larger family of MS class of ion channels encompassing prokaryotes (bacteria and archaea) as well as cell-walled eukaryotes (fungi and plants). MscL and its homologues have been found to play an important role in osmoregulation of bacterial cells. Though the MS channels of bacteria have been thoroughly studied, little is known about the pharmacology of these channels. This thesis has one general aim, that is, to identify compounds which are able to gate and/or alter the gating of the MS channels of bacteria in particular, the MscL of E. coli. Using the patch-clamp technique, potential compounds mostly identified via in-silico techniques were examined to observe the effects on MscL reconstituted in artificial lipid membranes and MscS in giant bacterial spheroplasts. The compounds were tested for the ability to spontaneously gate the MscL and MscS and/or alter the Boltzmann distribution parameters of the MscL, indicative of an effect on the gating of MscL. Compounds showing potential as MscL activators were then examined for in-vivo effects using different growth assays. The effects of parabens, gallates, eriochrome cyanine R, brilliant green, deoxycholic acid are reported. Of these compounds, parabens and eriochrome cyanine R showed the most encouraging results. Identification of MS channel gate ligands not only benefits structural studies as tetrodotoxin has for the voltage-sensitive sodium channel, these compounds could also V potentially serve as base compounds for novel antibiotics which would target the MS channels of bacteria. Since the MS channels of bacteria serve as safety valves for the bacterium, gating during exposure to a hypo-osmotic challenge such as rain to release excessive cellular turgor, a pharmacological agent that could impair the gating of the MS channels releasing essential cytoplasmic osmolytes, would cause the growth impairment or death of the bacterium. With the rise in multi-drug resistant bacteria, continual development of novel antibiotics is crucial.