Metabolites 2012.2.303-336:doi:10.3390/metabo2020303 OPEN ACCESS metabolites ISSN2218-1989 www.mdpi.com/journal/metabolites/ Review A Historical Overview of Natural Products in Drug Discovery Daniel A.DiasSylvia Urbanand Ute Roessner Metabolomics Australia,School of Botany,The University of Melbourne,Parkville,Victoria 3010, Australia Sehool of Applied Senees (Discipline of Applied Chemistry)Health Inovation Research Institute(HIRi)RMIT University,G.P.O.Box 2476V,Melbourne,Victoria 3001,Australia Australian Centre for Plant Functional Genomics,School of Botany,The University of Melboure, Parkville,3010,Victoria,Australia *Author to whom correspondence should be addressed;E-Mail:ddias@unimelb.edu.au; Tel.:+61-3-8344-3318. Received:I March 2012:in revised form:31 March 2012/Accepted:31 March 2012/ Published:16 April 2012 Abstract:Historically,natural products have been used since ancient times and in folklore for the treatment of many diseases and illnesses.Classical natural product chemistry methodologies enabled a vast array of bioactive secondary metabolites from terrestrial and marine sources to be discovered.Many of these natural products have gone on to become current drug candidates.This brief review aims to highlight historically significant bioactive marine and terrestrial natural products,their use in folklore and dereplication techniques to rapidly facilitate their discovery.Furthermore a discussion of how natural product chemistry has resulted in the identification of many drug candidates:the application of natural product chemistry and finally adopting metabolomic profiling and dereplication approaches for the comprehensive study of natural product extracts will be discussed. Keywords:natural products;secondary metabolites;drug discovery;bioactivity: metabolomics;dereplication,plants;sponges;algae;fungi Metabolites 2012, 2, 303-336; doi:10.3390/metabo2020303 metabolites ISSN 2218-1989 www.mdpi.com/journal/metabolites/ Review A Historical Overview of Natural Products in Drug Discovery Daniel A. Dias 1,*, Sylvia Urban 2 and Ute Roessner 1,3 1 Metabolomics Australia, School of Botany, The University of Melbourne, Parkville, Victoria 3010, Australia 2 School of Applied Sciences (Discipline of Applied Chemistry), Health Innovations Research Institute (HIRi) RMIT University, G.P.O. Box 2476V, Melbourne, Victoria 3001, Australia 3 Australian Centre for Plant Functional Genomics, School of Botany, The University of Melbourne, Parkville, 3010, Victoria, Australia * Author to whom correspondence should be addressed; E-Mail: ddias@unimelb.edu.au; Tel.: +61-3-8344-3318. Received: 1 March 2012; in revised form: 31 March 2012 / Accepted: 31 March 2012 / Published: 16 April 2012 Abstract: Historically, natural products have been used since ancient times and in folklore for the treatment of many diseases and illnesses. Classical natural product chemistry methodologies enabled a vast array of bioactive secondary metabolites from terrestrial and marine sources to be discovered. Many of these natural products have gone on to become current drug candidates. This brief review aims to highlight historically significant bioactive marine and terrestrial natural products, their use in folklore and dereplication techniques to rapidly facilitate their discovery. Furthermore a discussion of how natural product chemistry has resulted in the identification of many drug candidates; the application of advanced hyphenated spectroscopic techniques to aid in their discovery, the future of natural product chemistry and finally adopting metabolomic profiling and dereplication approaches for the comprehensive study of natural product extracts will be discussed. Keywords: natural products; secondary metabolites; drug discovery; bioactivity; metabolomics; dereplication, plants; sponges; algae; fungi OPEN ACCESS