Novel C11 Amino Derivatives of Cryptolepine

308 Pages·2010·27.71 MB·English

Universidade de Lisboa
Faculdade de Farmácia

Novel C11 Amino Derivatives of
Cryptolepine
Synthesis and in vitro studies with DNA and haeme

João Paulo Martins Ferreira Lavrado

Doutoramento em Farmácia
(Especialidade em Química Farmacêutica e Terapêutica)

2010

Dissertação submetida à Faculdade de Farmácia da Universidade de Lisboa em
cumprimento dos requisitos para obtenção do grau de Doutor em Farmácia,

especialidade em Química Farmacêutica e Terapêutica

Novel C11 Amino Derivatives of

Cryptolepine

Synthesis and in vitro studies with DNA and haeme

Orientação:
Professor Rui Ferreira Alves Moreira
Doutora Maria Alexandra da Silva Paulo

João Paulo Martins Ferreira Lavrado

Lisboa
Faculdade de Farmácia

2010
Universidade de Lisboa

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Statement

This thesis represents my own work, performed in the Faculdade de Farmácia, Universidade de Lisboa,
Portugal, and in the School of Pharmacy and Pharmaceutical Sciences, University of Manchester, U.K., and where
work was done in collaboration with other researchers a statement of the fact is made.
No portion of the work referred to in the thesis has been submitted in support of an application for another
degree or qualification of this or any other university or other institute of learning. Part of the work here presented
has been already published or submitted for publication (see appendix L).

Copyright Statement

The author and the (co-)promoters give the authorization to consult and to copy parts of this thesis for personal
use only and made only in accordance with instructions given by the author and lodged in the library of Faculdade de
Farmácia, Universidade de Lisboa This page must form part of any such copies made. Any other use is limited by the
Laws of Copyright, specially the obligation to refer the source whenever results from this thesis are cited
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Acknowledgments

I would like to express my gratitude to my supervisors Prof. Rui Moreira and Dr. Alexandra Paulo for
their sage advice, insightful criticism, and patient encouragement aided my Ph.D. progress in innumerable ways.
I am also very grateful to Prof. Kenneth Douglas and Dr. Elena Bichenkova, University of Manchester,
for all their help, advice and assistance in the studies with DNA and interpretation of results.
I would like to thanks Dr. Phil Rosenthal and Giri Gut, University of California, USA, for providing the
in vitro and in vivo antiplasmodial assays necessary to the development of this study.
I would like to thanks Dr. Maria M. Mota, Dr. Miguel Prudêncio and Dr. Ghislain Cabal, Unidade de
Malária, Instituto de Medicina Molecular, Universidade de Lisboa, for providing the in vitro antiplasmodial and
fluorescence microscopy assays imperious to the knowledge of antiplasmodial mode of action of the developed
compounds.
I am also very grateful to Dr. Cecília Díaz, Departamento de Bioquímica, Escuela de Medicina and
Instituto Clodomiro Picado, Universidad de Costa Rica, Costa Rica for the in vitro cytotoxicity studies of the
developed cryptolepine derivatives.
I would like to thanks Dr. Virgílio do Rosário and Dr. Dinora Lopes, Centro da Malária e Outras
Doenças Tropicais, IHMT, Universidade Nova de Lisboa, for provinding the in vitro cytotoxicity assays of the
developed quindolone derivatives.
I would also like to express my indebtedness gratitude to Fundação para a Ciência e Tecnologia for their
financial support (SFRH/BD/29202/2006), to the Faculdade de Farmácia, Universidade de Lisboa, Portugal and
Scholl of Pharmacy and Pharmaceutical Sciences, University of Manchester, UK by the availability of facilities,
material and equipment necessary to the development of this study.
I would like to thanks to Dr. Rita Guedes and Dr. Daniel Santos, Faculdade de Farmácia, Universidade de
Lisboa, for their help in the development of computational studies.
I wish also to thank to all the staff of the Faculdade de Farmácia, Universidade de Lisboa and in particular
to Francisco Carvalho and Ana Margarida Madureira for their help and humor.
I would also like express my deep gratitude to my family and friends for their great support during the
course of my study.
Last, but not least, I would like to thank to everyone who helped me along this theses in innumerous ways,
in particular to all who are and were my laboratory colleagues in Faculdade de Farmácia: Rita Capela, Tiago
Rodrigues, Cátia Ramalhete, Jalmira Mulchande, Maria Santos, Maria Teresa Dias, Patricia Rijo, Ana
Newton, Pedro Góis, Paulo Glória, Nuno Candeias, Marta Carrasco, Ana Ressurreição, Susana Lucas,
Praveen K. Siripuram, João Rosa, Alexandre Pinto, Pedro Cal, Francesco Montalbano, Nilsa Oliveira, Rudi
Oliveira and Sudarshan Reddy. R.
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Autobiography

Ph.D 2006-2010
Faculdade de Farmácia, Universidade de Lisboa, Portugal
Thesis Title: Novel C11 Amino Derivatives of Cryptolepine: Synthesis and in vitro studies with DNA
and Haeme.
Supervisors: Professor Rui Ferreira Alves Moreira; Doctor Alexandra da Silva Paulo.

M.Sc.in Pharmacy, (specialty Medicinal Chemistry), 2004 – 2006
Faculdade de farmácia, Universidade de Lisboa, Portugal
Thesis Title: Estudo da Síntese de Agentes Quimioterápicos.
Supervisors: Professor Rui Ferreira Alves Moreira

Degree in Chemistry (Licenciatura), 1998 – 2003
Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Portugal
Thesis Title: Distribuição e Reactividade de Mercúrio em Sedimentos do Estuário do Tejo
Supervisors: Doctor Ana Paula Paiva; Doctor João Alfredo Vieira Canário.
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