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Isolation, structure elucidation and biological investigation of active compounds in Cordia americana and Brugmansia suaveolens [Elektronische Ressource] / vorgelegt von Fabiana Cristina Geller

273 pages
Isolation, Structure Elucidation andBiological Investigation ofActive Compounds inCordiaamericanaandBrugmansiasuaveolensDissertationder Mathematisch-Naturwissenschaftlichen Fakultat¨der Eberhard Karls Universitat¨ Tubingen¨zur Erlangung des Grades einesDoktors der Naturwissenschaften(Dr. rer. nat.)vorgelegt vonFabiana Cristina Gelleraus Santa Cruz do Sul - BrasilienTubingen¨2010The research work described herein, was conducted under the supervision of Prof. Dr. Stefan Lauferin the Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Universityof Tubingen¨ from 01.01.07 to 31.08.10.Tag der mundlichen¨ Qualifikation: 10. November 2010Dekan: Prof. Dr. Wolfgang Rosenstiel1. Berichterstatter: Prof. Dr. Stefan Laufer2. Prof. Dr. Irmgard Merfort(Albert-Ludwigs-Universitat¨ Freiburg)“Jesus said to them, I am the bread of life; whoever comes to me shall not hunger, and whoeverbelieves in me shall never thirst”. John 6:35“O segredo nao˜ e´ correr atras´ das borboletas, mas sim, cultivar o seu jardim para que elas venhamate´ voce.ˆ ” (Mario´ Quintana)Mama, Papa (in memoriam) and Djones for your love, patience and support atall times.AcknowledgmentsThe following is my appreciation to those people that in the past and present gave me the spiritand encouragement to start, conduct and complete this thesis, as well to those people who mademe feel at home in Germany.
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Isolation, Structure Elucidation and
Biological Investigation of
Active Compounds in
Cordiaamericana
and
Brugmansiasuaveolens
Dissertation
der Mathematisch-Naturwissenschaftlichen Fakultat¨
der Eberhard Karls Universitat¨ Tubingen¨
zur Erlangung des Grades eines
Doktors der Naturwissenschaften
(Dr. rer. nat.)
vorgelegt von
Fabiana Cristina Geller
aus Santa Cruz do Sul - Brasilien
Tubingen¨
2010The research work described herein, was conducted under the supervision of Prof. Dr. Stefan Laufer
in the Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, University
of Tubingen¨ from 01.01.07 to 31.08.10.
Tag der mundlichen¨ Qualifikation: 10. November 2010
Dekan: Prof. Dr. Wolfgang Rosenstiel
1. Berichterstatter: Prof. Dr. Stefan Laufer
2. Prof. Dr. Irmgard Merfort
(Albert-Ludwigs-Universitat¨ Freiburg)“Jesus said to them, I am the bread of life; whoever comes to me shall not hunger, and whoever
believes in me shall never thirst”. John 6:35
“O segredo nao˜ e´ correr atras´ das borboletas, mas sim, cultivar o seu jardim para que elas venham
ate´ voce.ˆ ” (Mario´ Quintana)Mama, Papa (in memoriam) and Djones for your love, patience and support at
all times.Acknowledgments
The following is my appreciation to those people that in the past and present gave me the spirit
and encouragement to start, conduct and complete this thesis, as well to those people who made
me feel at home in Germany. My thanks go to my family, colleagues, cooperation partners and
friends who accompanied me during this work, in particular ...
• I am very grateful to my supervisor, Prof. Dr. Stefan Laufer for his comprehensive support
in all phases of this work and for the excellent opportunity of being a PhD. student in his
department during my doctoral studies, in the last three years. For his insights and efforts
to construct this bridge between South Brazil, Freiburg and Tubingen.¨ Also for the financial
support allowing me the participation in conferences and academic activities in Europe and
in Brazil. His attention and motivation contributed to my personal and professional improve-
ment. “Prof. Laufer, vielen herzlichen Dank!”.
• I am specially thankful to Prof. Dr. Irmgard Merfort, Freiburg, and her group. Thanks
for your dedication concerning the cooperation project Brazil-Germany and for the generous
support allowing the execution of phytochemical and biological analysis in your department.
Also for your valuable advices and improvements concerning my work and for teaching me
a lot of things about Pharmacognosy.
• the members of my defense committee Prof. Dr. Rolf Daniels and Prof. Dr. Peter Ruth,
for their time to go through my dissertation and taking part of my final exam.
• “muchas gracias tambien al profesor del Costa Rica”, Prof. Dr. Renato Murillo, for in-
troducing me the complicated NMR topic in a very patient and uncomplicated form. Your
suggestions and discussion regarding the elucidation of the flavonol glycosides were indis-
pensable.
• “um grande muito obrigado” to Prof. Dr. Berta Heinzmann, from Santa Maria, Brazil.
Thank you for introducing me to the plant world and for the profitable afternoons during the
collection of plants. I will always remember the nice time with you and your group.
´• Prof. Dr. Erico Flores, who always supported our cooperation project, specially during the
extraction of the plant material at the Department of Chemistry, at the Federal University of
Santa Maria, Brazil.
• Prof. Dr. Oliver Werz and his group, for the good living, the gatherings and the use of
his laboratories and equipment. Specially, I would like to thank Bianca Jazzar and Daniela
Muller¨ for providing me technical assistance in the 5-lipoxygenase assays.• “ein grosses Dankeschon”¨ to Prof. Dr. Wolf Engels (Brasilien-Zentrum), who along with
Prof. Dr. Stefan Laufer made efforts to acquire financial support from the Ministry of
Science, Research and the Arts of Baden-Wurttember¨ g for the project involving Brazil and
Germany.
• “ein grosses Dankeschon”¨ to Dr. Rainer Radtke for the great time that we spent together in
Tubingen.¨ Thanks for reading my dissertation and for your suggestions and improvements.
• the botanists Dr. Solon Longhi and Dr. Gilberto Zanetti for the collection of the plants
Cordia americana and Brugmansia suaveolens.
´ ´• Marcio Fronza and Cleber Schmidt from the Department of Pharmaceutical Biology and
Biotechnology, University of Freiburg, for carrying out the scratch and NF-B assays. Ca-
tiguria, many thanks for the nice chats from time to time about research and also other
things. Thanks for reading my dissertation and for your suggestions. I am sure that we
became good friends. I appreciated that I had the chance to meet you here in Germany!
• “ein super Dankeschon¨ fur”¨ Stef, for your very sweet Swabian sentence “Fabi, es wird
scho”. Stef, many thanks for reading my dissertation, for your suggestions involving NMR
spectra, as well as for the chocolates and “Gummibarchen”¨ time! I hope that you will come
to visit me in Brazil.
• “ein grosses Dankeschon”¨ to Lisa Steinhauser for supporting me with the NMR spectra and
also for organizing the NMR measurements.
• Sabine for enjoying with me the rare sunshine time during the breaks at the university. Joe
and Mohamed thanks for the patience during the first steps with the flash chromatography.
Maissa thanks for your big smile. Thanks also for the nice time in the lab and also for the
friendship.
• Claudi and Frank for their time to perform the LC-MS measurements and for the nice chat
during the “Mittagspause” in the “Mensa”.
• Verena Schattel for conducting the molecular modeling studies and for providing the dock-
ing pictures.
• Mar´ cia Goettert and Katharina Bauer for carrying out the biological assays on p38,
JNK3 and TNF.
• our secretary Karin Ward for all solutions concerning the bureaucratic problems.• all my colleagues and the employees from our department who contributed to the realization
of my dissertation.
• “meu amor e meu alemao˜ preferido”' Djones; how can I thank you? You are the best thing,
the best person that Tubingen¨ brought me! Thanks for your love, patience, encouragement
and support.
• my lovely, wonderful and big Geller family, specially meine Mutti, for her love, for the
unconditionally support, even many times feeling the distance ... a thousand thanks for
everything!
• my parents-in-law for holding me up in many moments.
• my family and friends in Germany: Walter for the very nice time in Munchen¨ and in
the“Bayerische Wald”, Pedro, Sandra and Jorge, Birkner's thanks for the nice celebra-
¨tions together. Also for the forever Brazilian friends that Tubingen brought me: Melissa,
Lissi, Ana Carolina, Karina, for sure we will see us in Brazil and will miss the nice time
in Tubingen.¨
• my friends in Brazil, Julie, Ana Paula e Andressa. The friendship that keeps us together is
one of the greatest thing that ever happened to me.
• the Eberhard Karls University of Tubingen¨ and the Pharmacy Institute in Tubingen¨ for
supporting the necessary conditions for the development of this research work and also for
the opportunity to attend German courses in order to improve my language skills.
• the Goverment of Baden-Wurttember¨ g (Zukunftsoffensive IV “Innovation und Exzel-
lenz”, Forderung¨ von internationalen Kooperationen zwischen den Hochschulen) for the
financial support that was indispensable for the development of this work.
Fabiana Cristina Geller

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