Synergy of intercalation and coordination binding to design novel DNA-targeting antineoplastic metallodrugs
Roy, Sudeshna
Citation
Roy, S. (2008, November 25). Synergy of intercalation and coordination binding to design novel DNA-targeting antineoplastic metallodrugs. Retrieved from
https://hdl.handle.net/1887/13281
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden
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Résumé
Sudeshna Roy was born in Midnapore (West Bengal, India) on November 20th, 1976. She finished both secondary and higher secondary education at the Mission Girls’
High School in Midnapore. She commenced her bachelor studies in Science with Honours in Chemistry in 1997 at Midnapore College. After successful completion, she joined Masters in Science with Inorganic Chemistry as specialisation. Her master’s project was based on Schiff-base ligand synthesis, followed by synthesis of copper complexes.
The post graduate research project was entitled as ‘Synthesis and characterisation of higher nuclearity organometallic clusters containing carbene moiety’ with national scholarship awarded by Council of Scientific and Industrial Research (CSIR) in the Indian Institute of Technology, Bombay (India). She was affiliated to Leiden University as a PhD student from April 2004 to September 2008 under supervision of Prof. Dr. J. Reedijk to pursue the doctoral research on anticancer ruthenium and platinum compounds.
This four year of research work has been presented in this thesis entitled as
‘Synergy of intercalation and coordination binding to design novel DNA-targeting antineoplastic metallodrugs’. During the PhD tenure she supervised one bachelor and three master students for their bachelor and master projects, respectively. Parts of the results described in this thesis have been presented at several national and international meetings, including the Gordon Research Conference: Metals in Medicine, 2006 at Oxford (U.K.), Holland Research School of Molecular Chemistry Symposium, 2006 at Leiden University (The Netherlands), 13th International Conference on Biological Inorganic Chemistry (ICBIC), 2007 at Vienna (Austria), COST D39/0005/11 Working Group Meeting, 2007 at Leiden (The Netherlands), COST D39, Working group meeting D39/0006:"Pt-based Metallodrugs; beyond Cisplatin and its Analogues", 2007 at Verona (Italy) and the Xth International Symposium on Platinum Coordination Compounds in Cancer Chemotherapy (ISPCC), 2007 at Verona (Italy).
Publications
Publications till date:
1. The square-planar cytotoxic [CuII-(pyrimol)Cl] complex acts as an efficient DNA cleaver without reductant
Maheswari P.U.; Roy S.; den dulk H.; Barends S.; van Wezel G. P.; Kozlevar B.;
Gamez P.; Reedijk J.
Journal of the American Chemical Society, 2006,128 (3), 710-711
2. Structure, cytotoxicity and DNA cleavage properties of the complex [CuII(pbt)Br2] Maheswari P.U.; van der Ster M.; Smulders S.; Barends S.; van Wezel G. P.; Massera, C.; Roy S.; den dulk H.; Gamez P.; Reedijk J.
Inorganic Chemistry, 2008, 47 (9), 3719-3727.
3. Derivatized phenanthrolines with improved selectivity as DNA-targeting anticancer or antimicrobial drugs
Roy S.; Hagen K.; Maheswari P.U.; Lutz, M.; Spek A.L.; van Wezel G. P.; Reedijk J.
ChemMedChem 2008, 3, 1427-1434.
Publications under preparation:
DNA interaction studies of potential antitumor platinum pyrimidine and pyridine complexes
Roy S.; Weatmaas J. A.; Hagen K.; van Wezel G. P.; Reedijk J.
(MS under preparation)
Comparison of cytotoxicity, cleavage property and DNA interaction by changing the central metal coordination
Roy S.; Maheswari P. U.; den dulk H.; Barends S.; van Wezel G. P.; Hartl, F.; Lutz, M.;
Spek A. L.; Gamez P.; Reedijk J.
(MS under preparation)
DNA cleavage and interaction study of a bifunctional Ru(II) complex
Roy S.; Maheswari P. U.; van Wezel G. P.; Kozlevar B.; Gamez P.; Reedijk J.
(MS under preparation)
Synthesis and DNA interaction of dinuclear complexes attached with a flexible linker Roy S.; van der Scilden K.; Reedijk J.
(MS under preparation)
Acknowledgment
I am forever indebted to my parents and my brother (always a shoulder to rest myself) for their unconditional moral support, endless love and motivation to take small steady steps. I let my heart speak the words to express my gratitude towards them silently.
We made a very strong-knitted family and this bondage inspired us to be brave enough to have a broad perspective to life, success and unavoidable failure. Education has been always the priority at home and still it remains that way making me proud of my upbringing. The words fall short for my best friend, bubu, to take steps together, to struggle together and to enjoy together. I don’t see myself anywhere without him.
In the spring of 2004, I started my Ph.D. as a member of the CBAC group in the Leiden Institute of Chemistry, Leiden University and the wonderful time here gave me the opportunity to get myself introduced to an amazing world of researchers, scientists, and professors.I am thankful to Leiden University and all the official and scientific stuffs for providing me the opportunity to start my research and continue it smoothly. I take this opportunity to express my sincere gratitude to all group members, “CBACers”. It has been a good experience collaborating with Uma and I express sincere thanks for introducing me to several biophysical measurements. The ‘pyramol’ project resulted into two chapters and I am indebted to her for sharing her expertise in this research field. Special thanks go to the “Ru-Pt” girls, Ariadna, Karlijn, Jolanda, Elena, Nuria and Patricia. I am deeply indebted to “Ari” and Nuria for being with me during crisis periods and nervous break- downs. The work meetings help me to learn intricate techniques of the fascinating synthetic inorganic chemistry and you all have been always there to have a chat about “chemistry”.
I have been working in my first year with Remy, Anja, Michiel and Eva, which enabled me to get familiar with a new work culture and interesting discussions about life in general. A very special mention for Geoff for his ‘no problem at all’ words, let it be computer related stuff or photography, crystal techniques to fancy presentation, paint shop to coffee and cookie. Thanks Geoff, you made my days to settle down and breathable. Hopefully you will remember my ‘may I ask you something?’ till now!! Katharine has been a wonderful colleague to work with and I am not missing this opportunity to thank her.
I sincerely acknowledge round-the-clock help from all group members. Patrick, you have been there always with crystal expertise and tiny details for handling them. All our secretaries, Yvonne, Ingrid and Marianne have been extremely helpful for all the official
issues and they always have an answer for me with smile on their faces. So, I knew there are someone who can help me without hesitation. John, you have been always kind to me with HPLC, mass (with dmso and dmf - stinky and toxic!!), safety, order, laptop, programmes, pictures (to name a few!) and a patient audience for my problems. You always have time and solution for tiniest problems. Jos, you always cheer me up with your hearty greetings. The fight with FAAS and ICP-OES was enjoyable with your continuous trials. I owe you a big hug. Jopie, without you three chapters would not have been in this thesis. Thanks a lot for your kind supply of ‘chloroterpy’ whenever I need and my conditional mass measurements (no dilution and no mixing!!) with samples most of the times submitted late. My sincere thanks go to Gé for all his helps, specially for EPR and valuable Sartorius filters. Without these equipment it would be difficult to work with such tiny quantity of platinum and ruthenium compounds. I am undoubtedly grateful to Hans, for letting me know the fine details of tissue culture and biological tests. The cytotoxicity assays have not been possible with his kind help by cell plate preparation, long discussion and suggestive planning of experiments. In the same note I would like to thank sincerely Kees and Fons. They have been of tremendous help for all NMR experiments with a smiling face to solve each small difficulty. For all CD experiments, Wim has been wonderful and very helpful with me. So I would like to extend my thanks to him. For all cytotoxicity assays Pharmachemie is being thanked sincerely. I am thankful to Dr. M. Lutz, Prof. A. L. Spek and Dr. B. Kozlevar for all the crystal structure determinations.
During these four years I have been introduced to multiple aspects of bioinorganic and coordination chemistry and the enrichment in knowledge has been possible for several group meetings and international conferences. My note of thanks reaches out for all the esteemed speakers. I would like to express my deepest gratitude to Prof. G. K. Lahiri for all the help, support and courage he gave me. To rescue me from all the complex bureaucracy and official paperwork, Esther van Delft has been extremely friendly and a saviour, my sincere thanks to her.
I would like to acknowledge the quality time I have spend with my ‘students’:
Paula, Joyce and Hakeem. The experience with you made me richer and gave me the pleasure to share my modest understanding of the subject. Special thanks go to Joyce for the excellent mutual motivation session and the tough “samenvatting”.
I have been lucky to have friends around me with constant ‘cheering up’ tonic.
Bhaiya-debjanididi being very special among them, Sarbanidi to motivate me to take a step
younger brother and Kartick making me feel comfortable for several issues. I would also like to thank Meenal and Nilesh bhaiya to ease a scared girl in a new environment.
Nalinabhada has been my vocal tonic and fighting partner for life, social issues and feminism, in addition a teacher who taught me how to work in a synthetic chemistry lab with precision and cleanliness. I would not forget Shiva and the kind family who embraced me with kindness and gave me chances to be home. This is the opportunity to utter ‘Thank You’ to all my flat-mates and my Dutch-mom, Evelyn for everything. All the support and positive words helped me to relax a little bit and encouraged me to move on.
