HHS Public Access Author Manuscript
HHS Public Access Author manuscript Author Manuscript Author ManuscriptMed Res Author Manuscript Rev. Author manuscript; Author Manuscript available in PMC 2017 January 01. Published in final edited form as: Med Res Rev. 2016 January ; 36(1): 32–91. doi:10.1002/med.21377. Strategies for the Optimization of Natural Leads to Anticancer Drugs or Drug Candidates Zhiyan Xiao1,2,*, Susan L. Morris-Natschke3, and Kuo-Hsiung Lee3,4,* 1Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China 2State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China 3Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599-7568, USA 4Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan Abstract Natural products have made significant contribution to cancer chemotherapy over the past decades and remain an indispensable source of molecular and mechanistic diversity for anticancer drug discovery. More often than not, natural products may serve as leads for further drug development rather than as effective anticancer drugs by themselves. Generally, optimization of natural leads into anticancer drugs or drug candidates should not only address drug efficacy, but also improve ADMET profiles and chemical accessibility associated with the natural leads. Optimization strategies involve direct chemical manipulation of functional groups, structure-activity relationship-directed optimization and pharmacophore-oriented molecular design based on the natural templates.
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