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2. VIDA INTERIOR: PSICANALISE E DESENVOLVIMENTO DA PERSONALIDADE;.

Author

Margot Waddell and Margot Waddell

Subjects
Personality, Developmental psychology, Psychoanalysis
Abstract

Seguindo as principais fases do desenvolvimento desde a infância até a velhice, a autora explora, de maneira lúcida, aspectos vitais das experiências que promovem crescimento mental e emocional, bem como daquelas que o impedem. Ao reunir uma ampla variedade de exemplos clínicos, não clínicos e literários, introduz de forma detalhada e acessível o pensamento psicanalítico contemporâneo, oferecendo uma abordagem vívida e pessoal à elusiva questão de como a personalidade se desenvolve.

Published
2017

3. Colaboradores

Author

Abbott, Nicholas J., Abdel-Razeq, Sonya S., Abdo, Tony, Afari, Maxwell Eyram, Agarwal, Sandeep, Al-Abid, Baha, Ali, Tanya, Aliotta, Philip J., Allen, Stephanie Michelle, Al Malki, Monzr M., Almeida, Rowena, Alqadi, Rasha B., Alvero, Ruben, Anderson, Mel L., Anderson, Thomas J.T., Andolina, Laura M., Andoscia, George F., Anilowski, Kathryn Taylor, Anthony, Anngene, Aoki, Etsuko, Aoun, Naim, Armstrong, Grayson W., Arzomand, Zuhal, Asiedu, Daniel K., Asif, Arif, Aulakh, Sudeep K., Avasare, Rupali, Babar, Tania B., Bachman, Emelia Argyropoulos, Baliog, Crisostomo R., JR, Bansal, Priya, Barré, Luke, Barrett, Trace, Basman, Craig L., Benner, Deanna, Berges, Arnaldo A., Bhagat, Vicky H., Bhatt, Harikrashna B., Bhatti, Danish, Biancuzzo, Rachael M., Bilodeau, Courtney Clark, Blakeney, Craig, Blomberg, Christopher P., Blood, Travis D., Bokshan, Steven L., Borowsky, Mark Eliot, Boske, Alexandra, Bouton, Tara C., Bowlby, Lynn A., Boyle, Madalene I., Brady, Mark F., Brar, Tina, Brennan, Keith, Brown, Elizabeth, Brown, Gavin, Brown, Kimberly M., Brown, Victoria, Buckley, Jennifer, Buffie, Alexandra, Burns, Jonathan, Burtis, D. Brandon, Burtt, Douglas, Bystrak, Tamara, Cabrera, Claudia Rodriguez, Cahill, Kate, Capobianco, Sara, Caraganis, Andrew, Carrubba, Aakriti, Castillo, Jorge J., Catana, Andreea M., Celestin, Frederic, Cerezo, Carolina S., Chalkely, Joshua, Chamberlain, Paul D., Chan, Philip A., Chapman, Arlene, Chen, Lily, Cheng, Vicky, Chisholm, Sarah L., Cholankeril, George, Cholankeril, Rosann, Cilia, Lindsey, Cohen, Lisa, Compton, Kaila, Copelin, Eddie L., II, Cramer, Meagan, Cristofaro, Patricia, Cunha, Joanne Szczygiel, Cunningham, Karlene, Curry, Stephanie A., Curtin, Alicia J., Dabhadkar, Kaustubh C., Dabiri, Ganary, Dalal, Deepan, Dalrymple, Kristy L., Danak, Shivang U., Das, Rituparna, Dasilva, Katia A., Dasilva, Manuel F., D’Avanzato, Catherine, Dawson, Melissa L., Defroda, Steven F., Degenhardt, Alexandra, De Souza, Andre Luiz, Diaz, Joseph A., Dionne, Emily, Doran, Amanda C., Duker, Andrew P., Eisenhower, Christine, Elia, Gregory, Ellsworth, Pamela, Epstein, Alan, Escarfuller, Juan A., Eskander, Michael A., Espinosa, Patricio Sebastian, Esteitie, Rania, Evans, Danyelle, Faber, Mark D., Fabre, Valeria, Fagan, Matthew J., Farooq, Fahad, Farooq, Muhammad, Farrell, Timothy W., Fayek, Mariam, Ferreira, Jason D., Ferri, Fred F., Ferri, Heather, Fontenot Ferriss, Amber N., Fine, Barry, Finney, Glen, Fischer, Staci A., Fong, Tamara G., Forcier, Michelle, Fort, Frank G., Fort, Glenn G., Fraser, Justin F., Friedman, Michael, Frisch, Daniel R., Gaddam, Sainath, Gallo, Anthony, Ganz, Michal, Garas, Marina, Garbus, Leanna R., Garneau, Edith, Geffert, Sara W.F., Gelfand, Samantha L., George, Paul F., Ghosh, Joydeep, Gilek-Seibert, Katarzyna, Gitelmaker, Dimitri, Gittings, Kimberly A., Goldberg, Richard J., Goldburt, Alla, Goldman, Jesse, Gordon, Paul, Graff, Nancy R., Grant, Frazer, Gray, John A., Griller, Nadia, Gringut, Simon, Grupke, Stephen L., Gultawatvichai, Patan, Guo, Canting, Gupta, Priya Sarin, Hack, Nawaz K.A., Hagau, Denisa, Haidemenos, Gregory M., Haim, Moti, Han, Leo, Handa, Sajeev, Harbord, Nikolas, Hardy, Erica, Harris, Andrew Paul, Harrison, Taylor, Hauser, Naomi, Hayes, Don, JR., Heitmiller, Dwayne R., Hejazi, Emily Z., Heung, Michael, Hines, Margaret R., Hochman, Brian, Hodax, Jonathan D., Hoffman, R. Scott, Hogan, Dawn, Holland, N. Wilson, Hume, Anne L., Huynh, Donny V., Huynh, Terri Q., Insalaco, Louis, Ismail, Ahmad M., Jain, Vanita B.D., Janigian, Robert H., Javier, Noelle Marie C., Johnson, Courtny, Johnson, Michael P., Jolley, Stacey M., Jolly, Angad, Jones, Kimberly, Joshi, Shyam, Kachroo, Naveen, Kalanithi, Lucy, Kapoor, Siddharth, Kass, Joseph S., Katz, Emily R., Kawata, Hiro, Kazim, Ali, Kedar, Sachin, Kelepouris, Ellie, Kellerman, Paul S., Kelly, Susan, Kern, Christopher R., Khalid, Naushaba Ishrath, Khan, A. Basit, Kim, Byung, Kimble, Brandi, Kirchner, Robert M., Klebanoff, Jordan, Kohn, Robert, Kokkirala, Aravind Rao, Kolte, Dhaval, Konstantino, Yuval, Kopyt, Nelson, Kostroun, Katherine, Kovalevsky, George, Krishnamohan, Prashanth, Kurss, David I., Lacamera, Peter, Lacasce, Ann S., Lakhani, Alisha, Lakin, Ashley, Lam, Uyen T., Latif, Syed R., Leavitt, David A., Lee, Kachiu C., Leis, Paul, Leopold, Beth Hilary, Levchenko, Andre, Li, Jian, Lightner, Donita Dillon, Lo, Patricia W., Long, Richard, Lowenhaupt, Elizabeth A., Luciano, Randy L., Lunghar, Layola, Maciag, Michelle C., Magee, Susanna R., Mahboob, Durkhani, Majczak, Marta, Majmudar, Shefali, Makai, Gretchen, Malhotra, Pieusha, Manjrekar, Eishita, Mansfield, Abigail K., Mariorenzi, Michael C., Matson, Kelly L., Mazumdar, Maitreyi, Mbuyi, Nadine, Mcculloh, Russell J., Mcguirk, Barbara, Medlin, Erin E., Meharg, Joseph, Mehta, Akanksha, Merriman, Jennifer B., Michaud, Gaetane, Minami, Taro, Minhas, Hassan M., Mirza, Farhan A., Mohiuddin, Naushaba, Morgan, Theresa A., Mughal, Aleem, Mukkamalla, Shiva Kumar R., Najem, Catherine E., Naqvi, Bilal H., Naseri, Hussain Mohammad H., Nasir, Uzma, Natan, Shaw, Nayer, Ali, Nazzal, Lama, Neithardt, Adrienne B., Nothnagle, Melissa, Novak, James E., Noyes, Adam M., Nsereko, Patrick, Nunneley, Chloe Mander, O’Brien, Gail M., Oesterle, Daniel W., Olawaiye, Alexander B., Olszewski, Adam J., Orchowski, Lindsay M., Pace, Paolo G., Pacheco, Cristina Antonio, Pan, Chris W., Pappas-Taffer, Lisa K., Parikh, Sarika, Patel, Bhavin C., Patel, Birju B., Patel, Janaki, Patel, Nima R., Patel, Pranav M., Patel, Saagar N., Patrick, Brett, Patterson, Alison, Paul, Grace Rebecca, Pesta, Lynn, Phillips, Katharine A., Picerno, Toni, Pickett, Christopher, Plante, Wendy A., Plumley, Kevin V., Pohlen, Michael, Polensek, Sharon S. Hartman, Posner, Donn, Pressman, Amanda, Promrat, Kittichai, Punjani, Shahnaz, Qawi, Imrana, Radlinski, Heidi, Rafelson, William M., Rafeq, Samaan, Ramakrishnan, Reshma, Rao, Meghana, Rasla, Somwail, Rathore, Bharti, Rathore, Ritesh, Raukar, Neha P., Reagan, John L., Reddy, Bharathi V., Reddy, Chakravarthy, Reddy, Snigdha T., Reginato, Anthony M., Regnante, Richard, Reid, Daniel Brian Carlin, Reus, Victor I., Ricci, Melissa, Rich, Harlan G., Richards, Rocco J., Righi, Giulia, Rinko, Rebecca, Rintels, Peter, Rivera, Alvaro M., Roberts, Nicole A., Rodriguez, Nicolette J., Rogers, Jamison, Roth, Julie L., Rougas, Steven, Rubeor, Amity, Ruenger, Thomas M., Ruhstaller, Kelly, Ryan, Hayley, Sadiq, Immad, Sahai, Tanmay, Saks, Emily K., Sampat, Radhika, Samtani, Sonia R., Satpathy, Hemant K., Satpathy, Ruby K., Sayeed, Syeda M., Scaramangas-Plumley, Daphne, Schmitt, Heiko, Schultz, Claire, Sciscione, Anthony, Sell, Peter J., Sepe, Steven M., Serrano, Claudia, Seshasai, Rebecca Kurnik, Shah, Kalpit N., Shah, Sanjeev R., Shah, Shivani, Shill, Jessica E., Shingina, Alexandra, Shlossman, Philip A., Shrestha, Asha, Sigman, Mark, Silverstein, Jared A., Silvia, Joanne M., Simon, James F., Singasani, Reddy, Singhal, Divya, Skalecki, Jon, Skylar-Scott, Irina A., Sladky, John, Smalls, Arlene J., Smith, Erin, Smith, Jeanette G., Smith, Jonathan H., Smith, Thomas, Sobel, Andrew D., Sohur, U. Shivraj, Soinski, Rebecca, Soler, Maria E., Soman, Sandeep, Souther, Scott M., Steinberg, Peter L., Steiner, Johannes, Stockwell, Philip, Stone, Lara, Sudhakar, Padmaja, Sushereba, Elizabeth, Sutter, Mary Beth, Swaminathan, Arun, Sweeney, Joseph, Syed, Wajih A., Tabba, Maher, Tammaro, Dominick, Tellioglu, Tahir, Thakkar, Jigisha P., Thomas, Anthony G., Thome, Andrew P., JR, Tibbetts, Erin, Tien, Alexandra Meyer, Tien, David Robbins, Tong, Iris L., Treon, Steven P., Trivedi, Hirsh D., Tryforos, Margaret, Tsukada, Hisashi, Tucci, Joseph R., Tukey, Melissa H., Uduman, Junior, Uiterwyk, Sean H., Ullrich, Nicole J., Umanath, Kausik, Vakili, Babak, Van Kirk, Emily, Vanvalkinburgh, Danny H., Vaughan, Jennifer E., Verma, Pooja, Villafuerte, Jorge A., Waase, Marc Paul, Waddell, Joel P., Wagner, Brent T., Weinberg, Adam J., Weiss, Emma H., Welesko, Mary-Beth, Weppner, Dennis M., Whitlatch, Hilary B., Whitney, Estelle H., Wicklund, Matthew P., Winchester, James F., Wincze, Jeffrey P., Wincze, John P., Wolpert, Marlene Fishman, Wu, Tzu-Ching (Teddy), Wylie, John, Yang, Nicole B., Yee, Jerry, Yessayan, Lenar Tatios, Yip, Agustin G., Young, John Q., Yu, Katherine M., Yuvienco, Candice, Zadzielski, Elizabeth, Zaheer, Fariha, Zenlea, Talia, Zimmerman, Mark, Zimmermann, Bernard, and Zuzek, Ryan W.

Published
2019
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5. Colaboradores

Author

Ahn, Henry, Alami, Ghassan B., Altamimi, Sahal, Athwal, George S., Berry, Greg K., Bhandari, Mohit, Blachut, Piotr A., Boyle, Richard A., Broekhuyse, Henry M., Buckley, Richard E., Coles, Chad P., Duffy, Paul J., Dust, William N., Evans, Alun, Gofton, Wade, Goldstein, Christina, Graham, Chris, Guy, Pierre, Hall, Jeremy A., Harvey, Edward J., Hickey, Michael A., Jenkinson, Richard, Kelly, Michael, King, Graham J.W., Kreder, Hans J., Kuzyk, Paul R.T., Lafl amme, G. Yves, Lawendy, Abdel-Rahman, Lefaivre, Kelly A., Leighton, Ross K., Liew, Allan S.L., MacLeod, Mark D., Malish, Dean G., Mandel, Scott J., March, Gerard, Martin, Rod, Martineau, Paul A., Mascarenhas, Randy, Mathew, Paul K., McCormack, Robert G., McKee, Michael D., O’Brien, Peter J., Panagiotopoulos, Kostas P., Papp, Steven, Petrisor, Brad, Pilkey, Brad, Reindl, Rudolf, Rouleau, Dominique M., Rouleau, Marie-Ève, Sanders, David W., Schemitsch, Emil H., Sharma, Rajrishi, Stephen, David J.G., Stone, Trevor B., Tadros, Ayman M., Talbot, Max, Vernon, James, Waddell, James P., Weber, Don W., White, Neil J., and Yach, Jeff

Published
2012
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6. Haberman Star Teacher Interview as a predictor of success in urban teacher preparation

Author

Jennifer H. Waddell and Jacob M. Marszalek

Subjects
urban teacher education, teacher education preparation, recruitment and retention, selectivity, quantitative research, Education
Abstract

In urban schools, along with skills for effective teaching, successful teachers must also possess values and belief systems conducive to teaching effectively in diverse settings (Becker, Kennedy, Hundersmarck, 2003; Haberman, 2008; Metzgar Wu, 2008). As demonstrated in CAEP standard 3, there is a critical need for EPPs to admit candidates who have both the dispositions to be effective teachers in urban schools and the propensity for success within the preparation program. The Haberman Star Teacher Interview is a commercial teacher selection instrument designed for use in selecting teachers for urban schools. This study examines the validity of the instrument as a selection instrument for teacher preparation programs. The selection instrument was administered to 109 students before entry into an urban teacher preparation program at an urban university in the U.S. Midwest. Inter-rater agreement and principle components analysis provided evidence of reliability and structural validity of the multi-part Haberman scores. Logistic regression analyses supported the validity of using the Haberman scores to predict later program attrition, but not in the manner recommended by its developers. Within this paper, the authors recommend the cautious use of the instrument in urban teacher preparation. Application of scoring and program implications are discussed.

Published
2018
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7. Cicerchia, Ricardo (director-compilador), Caminos de fierro…Tren a Bolivia. El ramal San Salvador de Jujuy-La Quiaca en la primera mitad del Siglo XX

Author

Jorge Waddell

Subjects
Industries. Land use. Labor, HD28-9999, Economic history and conditions, HC10-1085
Abstract

Cicerchia, Ricardo (director-compilador), Caminos de fierro…Tren a Bolivia. El ramal San Salvador de Jujuy-La Quiaca en la primera mitad del Siglo XX, Rosario, Prohistoria Ediciones, 2013 (208 págs.), ISBN: 978-987-1855-45-2

Published
2015

8. Presentación

Author

JORGE EDUARDO WADDELL

Subjects
Industries. Land use. Labor, HD28-9999, Economic history and conditions, HC10-1085
Published
2013

9. El mecanismo de control del capital de las empresas ferroviarias a partir de la Ley Mitre

Author

JORGE EDUARDO WADDELL

Subjects
Industries. Land use. Labor, HD28-9999, Economic history and conditions, HC10-1085
Abstract

La ley Mitre de 1907 estableció una nueva política ferroviaria que básicamente consistía en que los ferrocarriles sean explotados por empresas privadas, mayoritariamente británicas, y que las mismas sean rentables para remunerar el capital y para seguir invirtiendo en el sistema. La ley le daba algunas ventajas a las empresas pero establecía la intervención en las tarifas en caso de que la rentabilidad alcanzase determinado índice durante tres años. Por ello para el cálculo de la tasa de rentabilidad era imprescindible fijar el capital invertido por las empresas. La Dirección de Ferrocarriles era el organismo encargado de esta tarea. El estudio del capital comenzó en 1908 y avanzó hasta 1910. Los ejercicios de 1911 y 1912 se trabaron en una discusión sobre partidas que debían excluirse y a partir de allí no hubo interés ni del gobierno ni de las empresas de establecer el capital lo que se hizo con bastante tardanza y casi para llenar una formalidad. El artículo analiza el funcionamiento de este mecanismo en el Ferrocarril del Sud y en cuatro otras empresas. Abstract The law Mitre 1907 established a new railway policy, which basically consisted of railways operated by private companies, mainly British, and they are profitable to remunerate the capital and to continue to invest in the system. The law of gave some advantages to companies but established intervention rates where profitability reached certain index over three years. So for the calculation of the rate of return was essential to fix the capital invested by the companies. The railway Bureau was the body responsible for the task. The study of capital began in 1908 and advanced until 1910. 1911 And 1912 exercises developed into a discussion of items that should be excluded, and from there, there was no interest neither the Government nor the companies to establish the capital what was done with considerable delay and almost to fill a formality. The paper analyses the operation of this mechanism in the Southern Railway and four other companies.

Published
2013

11. A boneca

Author

Charles Waddell Chesnutt

Subjects
Language. Linguistic theory. Comparative grammar, P101-410, Literature (General), PN1-6790
Abstract

Tradução da obra de Charles Waddell Chesnutt Supervisão e revisão da tradução: Antony Cardoso Bezerra

Published
2009

13. Atividade antimicobacteriana in vitro de lactonas sesquiterpênicas e investigação do seu mecanismo de ação

Author

Wildner, Letícia Muraro, Universidade Federal de Santa Catarina, Bazzo, Maria Luiza, and Waddell, Simon J.

Subjects
Agentes antiinfecciosos, Tuberculose, Farmácia, Mycobacterium tuberculosis, Lactonas
Abstract

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmácia, Florianópolis, 2016. Introdução: A Tuberculose (TB) é uma doença infectocontagiosa considerada um problema global de saúde pública. A terapia em longo prazo, somada aos efeitos adversos dos medicamentos, contribui para a não adesão do paciente, o que resulta em falência do tratamento e seleção de linhagens de Mycobacterium tuberculosis resistentes. Por isso, a pesquisa e desenvolvimento de novos fármacos, que permitam a redução do tempo de tratamento e sejam uma alternativa para o tratamento de cepas resistentes, são considerados urgentes. Produtos naturais representam importantes fontes para o desenvolvimento de novos fármacos. A atividade antimicobacteriana já foi relatada para diversos compostos pertencentes a diferentes classes químicas, isolados de plantas, fungos e organismos marinhos, o que estimula a pesquisa de novos fármacos para o tratamento da TB provenientes de fontes naturais. Objetivos: Avaliar atividade antimicobacteriana in vitro de extratos e compostos naturais isolados de Calea uniflora e Calea pinnatifida e investigar seu mecanismo de ação. Métodos: Inicialmente, foi realizada uma triagem de 10 extratos e 11 compostos isolados obtidos das plantas Calea uniflora e Calea pinnatifida quanto à atividade antimicobacteriana in vitro frente a cepas referência de M. tuberculosis, Mycobacterium avium e Mycobacterium fortuitum, em concentrações entre 1,56 µg/mL e 100 µg/mL. Sete lactonas sesquiterpênicas (LS) apresentaram os melhores resultados e foram escolhidas para seguimento dos estudos da atividade antimicobacteriana in vitro, além da realização de análises in silico e estudo do seu mecanismo de ação, por meio da avaliação do perfil transcricional de M. tuberculosis após o tratamento com os compostos. Resultados: As LS (LS01 a LS07) apresentaram atividade antimicobacteriana frente a M. tuberculosis em fase exponencial de crescimento, de modo tempo e dose dependentes, com concentração inibitória mínima (MIC) variando de 6,25 µg/mL a 25 µg/mL. LS06 e LS07 também apresentaram atividade frente a M. tuberculosis em estado não-replicativo, em concentrações correspondentes a 4xMIC e 8xMIC, respectivamente. Nenhum dos compostos apresentou atividade frente a M. avium e M. fortuitum. Quando testados frente a isolados clínicos resistentes aos fármacos, os compostos apresentaram MIC semelhante às obtidas com os isolados sensíveis. Quando em combinação com isoniazida (INH) e rifampicina (RMP), os compostos não apresentaram sinergismo nem antagonismo. Os índices de seletividade variaram entre 1,77 a 11,88 em células de linhagem pulmonar MRC5. LS01, L06 e LS07 também apresentaram atividade frente a bacilos intracelulares, em modelo de infecção de macrófagos e demonstraram capacidade de proteção às células infectadas em concentrações correspondentes à MIC. Já quando em concentrações superiores, apresentaram citotoxicidade. Quando testada em estrutura granuloma-like, LS01 foi capaz de reduzir a contagem de unidades formadoras de colônia (UFC) na concentração 100 µM. As predições in silico indicaram que as LS estudadas neste trabalho podem apresentam boa biodisponibilidade por via oral, entretanto, podem sofrer intenso metabolismo de primeira passagem e apresentar altas taxas de ligação a proteínas plasmáticas. A análise do perfil transcricional de M. tuberculosis após o tratamento com LS01, LS06 e LS07 sugere que sua resposta pode estar relacionada à geração de espécies reativas de oxigênio (EROs), o que foi confirmado posteriormente, pela detecção de H2O2 em culturas de M. tuberculosis tratadas com os compostos. Este perfil também pode estar associado à habilidade das LS de se ligar aos resíduos de cisteína presentes em proteínas e no micotiol. Conclusão: Os compostos LS01-LS07 apresentaram boa atividade antimicobacteriana in vitro e parecem ter um novo mecanismo de ação quando comparadas aos fármacos utilizados atualmente no tratamento da TB e àqueles que se encontram em estudo clínico. Abstract : Background: Tuberculosis (TB) is a serious public health problem worldwide with one-third of the world´s population estimated to be infected with Mycobacterium tuberculosis. TB treatment requires the use of multiple drugs for at least 6 months. This lengthy drug therapy and adverse reactions to the drugs contribute to patient non-compliance, resulting in treatment failure and emergence of M. tuberculosis drug-resistant strains. There is an urgent need for new drugs to treat TB and natural products represent an important source for drug discovery. Several chemical classes of compounds isolated from plants, fungi and marine organisms have been described as potential antitubercular drugs, stimulating the search for new antimycobacterial agents isolated from natural sources. Aims: To evaluate the in vitro antimycobacterial activity of plant extracts and isolated plant-derived compounds from Calea uniflora and Calea pinnatifida and investigate their mode of action. Methods: A primary screening was conducted with 10 extracts from C. uniflora and C. pinnatifida and 12 purified compounds against M. tuberculosis, Mycobacterium avium and Mycobacterium fortuitum at concentrations ranging from 1.56 to 100 µg/mL. Seven sesquiterpene lactones (LS) showed the best results and were chosen for following studies on the in vitro antimycobacterial activity and also for in silico tests and transcriptional profiling analysis, in order to investigate their mode of action. Results: The LS (LS01-LS07) showed antimicrobial activity against log phase M. tuberculosis in a time- and concentration- dependent manner, with minimum inhibitory concentration (MIC) ranging from 6.25 to 25 µg/mL. LS06 and LS07 were also active against non-replicating M. tuberculosis at 4xMIC and 8xMIC, respectively. None of the compounds were active against M. avium and M. fortuitum. When tested against MDR M. tuberculosis clinical isolates, the compounds showed similar MIC compared to the sensitive isolates. They did not show synergism nor antagonism in combination with isoniazid or rifampicin. The selectivity index ranged from 1.77 to 11.88 in MRC5 lung cell line.LS01, LS06 and LS07 were also active against intracellular M. tuberculosis and were able to protect the infected cells at their MIC. Higher concentrations were found to be cytotoxic. When tested in a granuloma-like structure, LS01 reduced de colony forming units (CFU) counting at 100 µM. In silico studies indicate that these compounds may have good oral bioavailability, but intense first pass metabolism and high rates of plasma proteins binding. The transcriptional profiling analysis showed the response to LS01, LS06 and LS07 may be related to reactive oxygen species (ROS) generation, which was confirmed by the detection of H2O2 in M. tuberculosis cultures treated with the compounds. This response also may be related to the ability of the LS to bind to cysteine residues present in proteins and mycothiol. Conclusion: The LS 01-07 showed good in vitro antimycobacterial activity and seem to have a novel mode of action compared to the drugs currently used for the TB treatment and compared to the TB pipeline, which made them promising molecules for further studies.

Published
2016

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