Marcus A. Tius, PhD, MS
- Deputy Director, Professor
- Joanna L. Sullivan Distinguished Professor in Cancer Research
Natural Products and Experimental Therapeutics Program
University of Hawaii Cancer Center
Chemistry, College of Natural Sciences, University of Hawaii at Manoa
- PhD, MS, Chemistry
The focus of the research is in the area of organic synthesis, much of which has a cancer focus. Organic synthesis plays a pivotal role in drug discovery and also provides many of the tools for probing the molecular mechanisms of biochemical pathways. Most chemotherapeutic agents in current use against cancer are semisynthetic (e.g. taxol) or are completely synthetic (e.g. 5-fluorouracil). Even when the initial lead compound is a natural product, as it is in the case of taxol, the optimal drug often requires one or more chemical modifications. Organic synthesis is always required to determine the structural features of a drug molecule that are essential for activity, and is often necessary to elucidate the mechanism of action.
The Tius group does several kinds of research. (1) New methods development for efficient synthesis of natural products; (2) Application of these methods to the synthesis of natural products that have some cancer-relevant activity; (3) Collaboration with medicinal chemists and cancer biologists to develop new synthetic small molecules that may serve as leads for drug development. Areas of special interest are the synthesis and medicinal chemistry of cannabinoids, primarily classical-nonclassical hybrid structures, and the development of new versions of the Nazarov cyclization. A long-term collaboration with Dr. Alex Makriyannis (Director, Center for Drug Discovery, Northeastern University) has resulted in the discovery of new, selective, small molecule cannabinoid ligands. The CB2 cannabinoid receptor is implicated in immune regulation and CB2 antagonists up-regulate myeloid-derived suppressor cells leading to tumor suppression. The discovery in 2010 of a novel structural motif that confers exceptional CB2 selectivity on the cannabinoid ligand, resulting in a collaboration with Dr. Shu-Hsia Chen (Mt. Sinai).
A scaleable synthesis of rocaglamide, a plant-derived cytostatic small molecule, is underway. A variant of the asymmetric Nazarov cyclization discovered in the Tius group reaction has been used to prepare terpestacin, an anti-angiogenic natural product, and also a series of analogs that are being evaluated for activity by Center member Dr. Patricia Lorenzo. A number of clofazimine analogs have been prepared and are being evaluated as immune system modulators by Center member Dr. Reinhold Penner.
- "An Organocatalytic Asymmetric Nazarov Cyclization" Basak, A. K.; Shimada, N.; Bow, W. F.; Vicic, D. A.; Tius, M. A. J. Am. Chem. Soc. 2010, 132, 8266-8267.
"Enamine-Iminium Ion Nazarov Cyclization of ï¡-Ketoenones" Bow, W. F.; Basak, A. K.; Jolit, A.; Vicic, D. A.; Tius M. A. Org. Lett., 2010, 12, 440â443.
"Traceless Chiral Auxiliaries for the Allene Ether Nazarov Cyclization" Banaag, A. R.; Tius, M. A. J. Org. Chem. 2008, 73, 8133-8141.
"Total Synthesis of (Â±)-Terpestacin and (Â±)-11-epi-Terpestacin" Berger, G. O; Tius, M. A. J. Org. Chem. 2007, 72, 6473-6480.
Publication list via PubMed
- M.A. Tius, Principal Investigator
"Cyclopentannelation In Total Synthesis"
April 1, 2007-March 31, 2011
- R01 (A. Makriyannis at Northeastern University is Principal Investigator)
"Cannabinergic Ligands and Drugs"
April 1, 2008-March 31, 2013
- P01 (A. Makriyannis at Northeastern University is Principal Investigator)
"Endocannabinoid Active Sites as Therapeutic Target"
April 1, 2008-March 31, 2013