Triazaspiroalkenes as potential inhibitors of dihydrofolate reductase 1

TRIAZASPIROALKENES AS POTENTIAL INHIBITORS OF DIHYDROFOLATE REDUCTASE PAULINE ONG (B. Sc. (Hons), Universiti Teknologi Malaysia) A THESIS SUBMITTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DEPARTMENT OF PHARMACY NATIONAL UNIVERSITY OF SINGAPORE 2009 ACKNOWLEDGEMENTS I am deeply indebted to my supervisor A/Prof Chui Wai Keung, who has guided and supported me throughout my PhD study whilst allowing me the room to work in my own way. Thanks to A/Prof Chan Sui Yung, Head of Department of Pharmacy, for providing the facilities for this projects. Thanks to Medicinal Chemistry Program (Office of Life Science) and National University of Singapore for providing me the research scholarship. I will also like to thank Dr Gigi Chiu (Department of Pharmacy), A/Prof Prof Yao Shao Qin (Department of Chemistry and Biological Sciences) and Prof Bay Boon Huat (Department of Anatomy) for their guidance and precious opinion in our collaboration works. I am grateful to have Dr Ma Xiang as my senior. He helped me in many aspects of my study. Thanks to Dr Mahesh Uttamchandani for help and guidance in high throughput screening. Thanks to Miss Tan Bee Jen for guidance and advice in cell culture work. Thanks to Miss Ng Cheng Teng for her hard work in our collaboration project. I will like to show my gratitude to Miss Lye Pey Pey and Miss Ng Sek Eng from the Department of Pharmacy, Mdm Han from the Department of Chemistry, and Mr Toh Kok Kee and Miss Saw from the NUMI for providing technical support for my project. Thanks to Dr Bong Yong Koy, Miss Yang Hong, Miss Michelle Kok and all past and current members of A/Prof Chui’s Lab for their great companionship throughout the years of my life here. Special thanks to Dr Soh Chai Hoon, Miss Khoo Sook Kuen, Miss Sim Kae Shin, Miss Koh Ching Theng, Miss Leong Wei Lee, Ms Jessie Ng, NAT and all my friends for invaluable moral support and encouragement. I owe my deepest gratitude to my parents and my siblings, for always being there to support me. Lastly, I offer my regards and blessings to all of those who supported me in any respect during the completion of the project. Thank you very much. . TRIAZASPIROALKENES AS POTENTIAL INHIBITORS OF DIHYDROFOLATE REDUCTASE PAULINE ONG (B. Sc. (Hons), Universiti Teknologi Malaysia) A THESIS SUBMITTED FOR THE DEGREE OF. A/Prof Chan Sui Yung, Head of Department of Pharmacy, for providing the facilities for this projects. Thanks to Medicinal Chemistry Program (Office of Life Science) and National University of. to thank Dr Gigi Chiu (Department of Pharmacy), A/Prof Prof Yao Shao Qin (Department of Chemistry and Biological Sciences) and Prof Bay Boon Huat (Department of Anatomy) for their guidance and