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Fungal Cell Wall Disruption by Alkamides from Echinacea

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Fungal Cell Wall Disruption by Alkamides from Echinacea Fungal cell wall disruption by alkamides from Echinacea By Isabel Maria Linhares Cruz, B.Sc. A thesis submitted to The Faculty of Graduate Studies and Research in partial fulfilment of the degree requirements of (Master of Science) Department of Biology Carleton University Ottawa, Ontario, Canada (August 2011) Copyright © 2011-Isabel Cruz Library and Archives Bibliotheque et 1*1 Canada Archives Canada Published Heritage Direction du Branch Patrimoine de I'edition 395 Wellington Street 395, rue Wellington OttawaONK1A0N4 OttawaONK1A0N4 Canada Canada Your file Votre r4f6rence ISBN: 978-0-494-83172-4 Our file Notre r6f6rence ISBN: 978-0-494-83172-4 NOTICE: AVIS: The author has granted a non­ L'auteur a accorde une licence non exclusive exclusive license allowing Library and permettant a la Bibliotheque et Archives Archives Canada to reproduce, Canada de reproduire, publier, archiver, publish, archive, preserve, conserve, sauvegarder, conserver, transmettre au public communicate to the public by par telecommunication ou par I'lnternet, preter, telecommunication or on the Internet, distribuer et vendre des theses partout dans le loan, distribute and sell theses monde, a des fins commerciales ou autres, sur worldwide, for commercial or non­ support microforme, papier, electronique et/ou commercial purposes, in microform, autres formats. paper, electronic and/or any other formats. The author retains copyright L'auteur conserve la propriete du droit d'auteur ownership and moral rights in this et des droits moraux qui protege cette these. Ni thesis. Neither the thesis nor la these ni des extraits substantiels de celle-ci substantial extracts from it may be ne doivent etre imprimes ou autrement printed or otherwise reproduced reproduits sans son autorisation. without the author's permission. In compliance with the Canadian Conformement a la loi canadienne sur la Privacy Act some supporting forms protection de la vie privee, quelques may have been removed from this formulaires secondaires ont ete enleves de thesis. cette these. While these forms may be included Bien que ces formulaires aient inclus dans in the document page count, their la pagination, il n'y aura aucun contenu removal does not represent any loss manquant. of content from the thesis. •*• Canada "The important thing is not to stop questioning. Curiosity has its own reason for existing. One cannot help but be in awe when he contemplates the mysteries of eternity, of life, of the marvelous structure of reality. It is enough if one tries merely to comprehend a little of this mystery every day." Albert Einstein—From the memoirs of William Miller, an editor, quoted in Life magazine, May 2, 1955; Expanded, p. 281. Abstract The research presented in this thesis focuses on the study of the antifungal properties, mode of action and molecular structure-antifungal activity relationship of selected alkamides. Echinacea's antimicrobial and antioxidant activities, and its ability to modulate the immune cells activity have been demonstrated in several studies. The phytochemical composition of Echinacea is well established as a complex mix of caffeic acid derivatives, glycoproteins, polysaccharides and the lipophilic alkamides. The complexity of the extract composition makes it difficult to determine if the pharmacological effects of Echinacea preparations are caused by a specific compound, a class of compounds or are the result of the many constituents acting synergistically. However, new insights concerning the membrane permeability, bioavailability and molecular mode of action, have renewed interest in the hypothesis that alkamides are implicated in the pharmacological effects of Echinacea. Alkamides are secondary metabolites widely distributed in plants and the major lipophilic compounds in Echinacea extracts. This large group of closely related unsaturated fatty acid amides are mostly derived from undeca and dodecanoic acids that differ by the length of the carbon chain, the degree of saturation, and position of saturated carbon bonds. Here I propose to test the hypothesis that the antifungal mode of action of Echinacea extracts is through the disruption of the yeast cell wall/membrane complex by alkamides. -Ill- Dedication Dedicatoria In memoriam In memoriam This dissertation is dedicated to my Esta dissertacao e dedicada a minha mae mother Maria Jose Linhares Cruz, to my Maria Jose Linhares Cruz, as minhas little sisters Artemara and Idjanira, and irmazinhas Artemara e Idjanira e ao irmao/irma que nao chegou a nascer e to a never born sibling I didn't have the que nao tive a oportunidade de conhecer. chance to get to know. I'm grateful for the Sou grata pelos poucos anos que passa- few years I shared their presence in this mos juntos nesta realidade. Saudades! realm. I miss you! This dissertation is especially dedicated Esta dissertacao e especialment dedicada ao meu pai Jose Artero Cruz, cuja vida to my father Jose Artero Cruz, whose foi encurtada por doenca cardiaca. life was cut short by heart disease. As a Quando menina tie infundiu em mim a little girl he stilled in me the confidence confianga necessdria para realizar os meus to live my dreams, such as this one. sonhos., como este aqui. Sua ausencia e His absence is deeply felt at this moment profundamente sentida neste momento of accomplishment in my life. de realizacao in minha vida. Dad was the best example of generosity, Meu pai foi o melhor exemplo de generosi- dignity, simplicity and honesty I ever dade, dignidade, simplicidade and honesti- knew. In truth, everything I know that dade que conheci. Na verdade, tudo o que matters in life I learned from him— A man aprendi de importante na vida aprendi of few but very wise words. Unfortunately, com meu pai—Um homem de poucas mas the ability to listen carefully and to say sdbias palavras. Infelizmente, dele eu nao just the essential is one thing I didn't herdei a qualidade de ouvir atentamente e take from my father. And I could have falar apenas o necessdrio, o que as vezes used it in some occasions! I am the most me faz falta! Me considero uma pessoa de sorte por ter sido sua filha querida e por fortunate to have been my "dad's little te-lo tido como exemplo de vida. girl" and to have had him as role model. -IV- Dedication To the Sunshines of My Life Aos Raios de Sol da Minha Vida Motherhood is one of the most rich and Ser mae e uma das experiencias mais profound experiences in a woman's life. profundas e ricas da vida de uma mulher. I dedicate this dissertation to my beau­ Dedico esta dissertacao aos meus lindos e tiful and beloved children, Flavio queridos filho efilha, Flavio Daniel Cruz Daniel Cruz Caracas and Gabriela Caracas and Gabriela Cruz Caracas. Cruz Caracas. I am so proud to be your Eu sou uma mae tao orgulhosa, amo voces dois imensamente! mother, I love you two dearly! This thesis is also dedicated to my life­ Esta tese tambem e dedicada ao meu long partner, husband, the love of my life, companheiro, esposo, amor da minha and above all my very best friend Flavio vida, e sobretudo meu melhor amigo, Caracas Jr. Thank you for being my part­ Flavio Caracas Jr. Obrigada por ser meu ner in all the ups and downs and ins and parceiro em todos os altos e baixos e outs of life including this project. This todos os "sobe-e-desce" da vida incluindo thesis is also yours, because without your este projeto. Esta tese e sua tambem patience, understanding and endless love porque sem a sua paciencia, compreen- sao e infinita afeicao, durante todo este throughout this entire process this work processo, este projeto nao teria nem would probably have not even started. comecado. Voce aturou muito sem nunca You put up with a lot without ever ques­ questionar a sensatez do meu sonho de tioning the wisdom of my dream of fazer meu mestrado. E finalmente, quero getting my Master's degree. And finally, Ihe pedir desculpas pela vida dos ultimos I want to tell you how sorry I am that trav­ anos, quando viagens e finais de semana elling and weekends have been put on hold foram sacrificados para que eu pudesse for the last few years of our lives so I could realizar mais uma conquista em minha achieve this goal in my academic pursuits. formacao academica. Prometo que, I promise that eventually, you will get your eventualmente, voce terd seu barco, afinal sailing boat; a canoe is still a boat right? canoa conta como barco, nao conta? -V- Acknowledgements Agradecimentos It is with immense gratitude that I thank E com imensa gratiddo que agradeco Dr. Myron Smith for the opportunity Dr. Myron smith pela oportunidade de to pursue my Master's degree under his realizar o meu mestrado sob a sua super- visdo e de me beneficiar de seu vasto supervision and to draw upon his vast conhecimento e experiencia. knowledge and experience. Besides his constant good nature and Alem de seu constante bom cardter e sua seemingly endless patience, one of aparentemente infinita paciencia, uma Myron's best attributes, is his ability to das melhores qualidades de Myron, e a sua habilidade de motivar e orientar motivate and offer sound advice in times em momentos criticos quando experi- of confusion, when experiments don't mentos nao dao o resultado esperado e go smoothly and frustration mounts; a frustracao se acumula; o que acontece which happens more often than not. com mais frequencia do que se imagina. His broad knowledge, positive feedback Seu vasto conhecimento, comentdrios and constructive criticism has guided positivos e criticas construtivas guiaram my research through many challenges a minha pesquisa atraves de muitos and difficulties, and yet I was always desafios e dificuldades, e mesmo assim eu treated as an equal.
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