COMPUTER PROGNOSIS OF BIOLOGICAL ACTIVITY FOR A NUMBER OF NEW 7-R-8-SUBSTITUTED-1,3-DIMETHYL-XANTHINE

AbstractCreation of new potential active pharmaceutical ingredients of synthetic origin is an urgent problem of modern medical chemistry. With this purpose was obtained a number of original 7,8-disubstituted theophylline, and some molecular and pharmacological descriptors are calculated using public Web-resource Chemicalize.org. There was shown the influence of respective substituents in 7 and 8 positions of molecules of synthesized substances on druglike and was confirmed the prospects of chosen area of study. Keywords: virtual analysis, 7,8-disubstituted 1,3-dimethylxanthine, druglike, Ghosh, Maggie and Weber filters.Â

ChemScanner: extraction and re-use(ability) of chemical information from common scientific documents containing ChemDraw files

We developed ChemScanner, a software that can be used for the extraction of chemical information from ChemDraw binary (CDX) or ChemDraw XML-based (CDXML) files and to retrieve the ChemDraw scheme from DOC, DOCX or XML documents. This can facilitate the reuse of chemical information embedded into diverse documents used as standard storage and communication instrument in chemical sciences (e.g. for student’s theses, PhD theses, or publications). The extracted information is processed to reactions, molecules, as well as additional text and values and can be accessed via the ChemScanner UI. ChemScanner supports the export to Excel and CML, the direct import of the extracted data to the Open Source ELN Chemotion or the use via “copy and paste” of selected information. The software was designed with a focus on the processing of documents with embedded molecular structure information as CDX or CDXML as these are the most common file formats for chemical drawings. The project aims to support the chemists in their efforts to re-use chemistry research data by providing them missing tools for an automated assembly of reaction data

The pH Dependent Interaction between Nicotine and Simulated Pulmonary Surfactant Monolayers with Associated Molecular Modelling

Pulmonary surfactant is an endogenous material that lines and stabilises the alveolar air-liquid interface. Respiratory mechanics can be compromised by exposure to environmental toxins such as cigarette vapour, which contains nicotine. This study aims to determine the influence of nicotine on the activity of simulated lung surfactant at pH 7 and pH 9. In all cases, the addition of nicotine to the test zone caused deviation in surfactant film performance. Importantly, the maximum surface pressure was reduced for each system. Computational modelling was applied to assess key interactions between each species, with the Gaussian 09 software platform used to calculate electrostatic potential surfaces. Modelling data confirmed either nicotine penetration into the two-dimensional structure or interfacial / electrostatic interactions across the underside. The results obtained from this study suggest that nicotine can impair the ability of pulmonary surfactant to reduce the surface tension term, which can increase the work of breathing. When extrapolated to gross lung function alveolar collapse and respiratory disease (e.g. chronic airway obstruction) may result. The delivery of nicotine to the (deep) lung can cause a deterioration in lung function and lead to reduced quality of life

MOLECULAR DOCKING STUDIES OF OPENED-CHAIN ANALOGUES OF ANTIMYCIN A ASCASPASES INHIBITORS OF APOPTOSIS IN COLORECTAL CANCER 3

Objective: Studies of open-chain analogues of antimycin A as caspase inhibitors of apoptosis by molecular docking approach through computeraideddrug design. The noveltyof this studyis finding the potentialantimycinA33 analogues which structurally modified against caspases.Methods: In finding potential caspase inhibitor of apoptosis in colorectal cancer (CRC) by in silico approach has been utilized. Protein structure ofcaspase has been downloaded from Protein Data Bank (1SHJ). The minimized of caspase was ready for molecular docking analysis. Analogues ofantimycin A as lead compounds were designed and assessed using Molsoft drug-likeness. Both protein and lignan derivatives were docked withAutodock 4.2. The best docking score was shown by the lowest binding energy.3Results: Analogues of antimycin A has been done by evaluating their physicochemical properties as lead compounds. From this assessment, itshowed that analogue 2 (AMD2), intermediate amide 4 (AMD4) showed good compounds to be drug-likeness by following Lipinski's rule of five(RO5), while intermediate amide 3 (AMD3) and antimycin A3 (AMY3) showed cannot followed in Lipinski's RO5. From molecular docking result, themost favorable binding of caspase was AMD4 and AMD2 based on its energy that AMD4 (−7.34 kcal/mol) has the best binding interaction comparedto AMD2 (−7.33 kcal/mol), AMY3 (−7.26 kcal/mol), and AMD3 (−5.23 kcal/mol), respectively.3Conclusion: This studies demonstrated that the opened-chain analogues of antimycin AAMD2 and AMD4 as a promising candidates of caspaseinhibitor of apoptosis in CRC.Keywords: Open-chain analogue, Antimycin A3, Caspase, Apoptosis, Anticolorectal cancer.3

Aplicação de membrana oca em um sistema de 96-Well plate para determinação de desreguladores endócrinos em água por HPLC

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas, Programa de Pós-Graduação em Química, Florianópolis, 2016.O objetivo deste trabalho foi o desenvolvimento de um método para determinação de seis desreguladores endócrinos (4-nonilfenol, 4-octilfenol, 4-terc-octilfenol, metilparabeno, etilparabeno e bisfenol A) empregando-se um sistema de 96-Well plate associado com a microextração por membrana líquida renovável usando membrana oca e cromatografia líquida de alta eficiência. O sistema de 96-Well plate permite que o analista realize até 96 extrações simultâneas, o que contribui em muito para uma melhor frequência analítica. Poços de amostragem foram utilizados para a realização da extração e dessorção. Neste estudo, o volume total de amostra em cada poço foi de 1,5 mL enquanto o volume de solvente de dessorção foi de 300 µL. O método proposto mostrou-se muito vantajoso, pois alcançou valores satisfatórios de detecção bem como também ganho de tempo nas análises. Além disso, pode-se citar uma eficiente limpeza da amostra e adequação do método ao instrumento analítico. Primeiramente foi estudada a relevância dos procedimentos com a membrana oca porosa, tais como o uso ou não de recobrimento na membrana, e a utilização ou não de solventes extrator e dispersor na amostra. A melhor condição encontrada foi o uso de recobrimento na membrana e o emprego de solvente extrator junto a amostra. Logo após, foram otimizadas as condições de dessorção. O tempo de dessorção foi avaliado na faixa de 10 a 30 min, sendo que a condição ótima foi de 10 min. O solvente de dessorção também foi estudado e o que obteve uma maior reposta foi a utilização de 75% de acetonitrila e 25% de água. O melhor solvente de recobrimento da membrana foi a mistura de 50% de 1-octanol e 50% de hexano. Dentre os solventes extratores avaliados, o hexano apresentou um melhor resultado. A faixa de pH estudada variou de 4 a 6, sendo 5 o pH ótimo para a extração. Por fim, foi realizado um planejamento de composto central para analisar o efeito da força iônica (adição de sal), volume de solvente extrator e tempo de extração sobre a eficiência de extração. As condições ótimas foram a não adição de sal (NaCl), 15 µL de solvente extrator e o emprego de 45 min de extração. A partir dos resultados obtidos foram realizadas curvas de calibração para a obtenção dos parâmetros analíticos de mérito. Os limites de quantificação variaram de 0,5 a 15 µg L-1. A HFRLM combinada com o sistema de 96-Well plate foi aplicada em amostra de água e foram obtidas recuperações entre 72 e 130% com RSD variando de 1 a 14,3%. Deste modo, a técnica mostrou boa sensibilidade e aplicabilidade para a determinação de parabenos, bisfenol A e alquilfenóis em amostras aquosas.Abstract : The present work aims to determine six endocrine disruptors (4-nonylphenol, 4-octylphenol, 4-terc-octylphenol, methylparaben, ethylparaben and bisphenol A) employing the 96-Well plate system associated with hollow fiber renewal liquid membrane and high-performance liquid chromatography. The 96-Well plate allows to the analyst to perform up to 96 simultaneous extractions, which increases considerably the analytical frequency. Sampling wells were used to perform the extraction and desorption. In this study, the total volume in each well was 1.5 mL while the volume of desorption solvent was 300 µL. The proposed method exhibited very advantageous for the reason that good analytical performance was achieved and analysis time was saved. Furthermore, an efficient clean-up of the sample and suitability of the method to the analytical instrument can be mentioned. Firstly, it was studied the relevance of the techniques, such as the use of recoating on the membrane and the use of extractor and disperser solvents. The best conditions achieved were the use of recoating on the membrane and the use of extractor solvent. After that, liquid desorption conditions were optimized, being the time between 10 and 30 min evaluated and the time of 10 min was chosen. The desorption solvent was also studied and it was obtained a greater response using 75% of acetonitrile and 25% of water. The best recoating solvent on the membrane was a mixture of 50% of 1-octanol and 50% hexane. Among the extractor solvents evaluated the hexane showed the best result. The pH of the sample was also investigated in the range of 4 to 6, being 5 the optimal pH. Finally, it was made a central compound planning to study the ionic strength, extractor solvent volume and extraction time. The optimal conditions were not adding salt, 15 µL of extractor solvent and 45 min of extraction. From these results it was prepared calibration curves to each analyte to obtain the statistical parameters and analytical figures of merit. The limit of quantification varied from 0.5 to 15 µg L-1. The HFRLM combined with the 96-Well plate was applied in water samples and recuperation from 72 to 130% were achieved with errors between 1 to 14,3%. Thus, this technique shows good sensibility and applicability to determination of parabens, bisphenol A and alkylphenols in aqueous samples

IN SILICO DOCKING STUDIES OF GALLIC ACID STRUCTURAL ANALOGUES AS BCL-XL INHIBITOR IN CANCER

Objective: Apoptosis, or programed cell death, forms an important part of the cellular regulation machinery. The Bcl-2 protein family, comprisingproapoptotic and antiapoptotic members, forms an important part of the cells internal apoptotic pathway. Overexpression of the antiapoptoticmembers of the family in a number of cancer cell lines renders them immune to apoptosis and the ability to survive under conditions of cellular stress.Inhibition of the antiapoptotic members of the Bcl-2 family like Bcl-XL is, therefore, an interesting target for the development of anticancer therapy.Methods: The structure of antiapoptotic Bcl-XL receptor (1YSG) was taken from PDB database. The 23-dimensional structure of gallic acid analogswas designed. The Lipinski properties of gallic acid analogs were calculated using molsoft. Docking studies have been carried out through Autodock4.0 software.Results: Molecular docking analysis with gallic acid and their structural analogs showed propyl gallate, benzyl gallate, diallyl gallate, phenyl ethylgallate, and allyl gallate are more interactive and binding strongly than gallic acid at active site of Bcl-XL.Conclusion: Further these five compounds should be considered as potential candidates for Bcl-XL inhibitor.Keywords: Apoptosis, Bcl-2, Antiapoptotic Bcl-XL receptor, Gallic acid, Docking studies