title: Evolutionary inspirations for drug discovery.
abstract: Conceptual innovations are needed to address the challenge of 'more investments, fewer drugs' in the pharmaceutical industry. Since the publication of The Origin of Species by Charles Darwin 150 years ago, evolution has been a central concept in biology. In this article, we show that evolutionary concepts are also helpful to streamline the drug-discovery pipeline through facilitating the discovery of targets and drug candidates. Furthermore, the antioxidant paradox can be addressed by an evolutionary methodology. Through examining the evolved biological roles of natural polyphenols (which dominate current antioxidant drug discovery), we reveal that polyphenols (particularly flavonoids) are not evolved for scavenging free radicals. This finding provides new clues to understanding why the strong in vitro antioxidant activities of polyphenols cannot be translated into in vivo effects. Polyphenols have evolved a superior ability to bind various proteins, so we also argue that they are good starting points for multi-target drugs.
authors: National Key Laboratory of Crop Genetic Improvement, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, P. R. China. zhy630@mail.hzau.edu.cn
authors: Hong-Yu
authors: HY
authors: Zhang
authors: Ling-Ling
authors: LL
authors: Chen
authors: Xue-Juan
authors: XJ
authors: Li
authors: Jian
authors: J
authors: Zhang
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D005075:Biological Evolution; D016503:Drug Delivery Systems; D015195:Drug Design; D055808:Drug Discovery / Q000266:history / Q000379:methods*; D004345:Drug Industry / Q000458:organization & administration; D005419:Flavonoids / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D049672:History, 19th Century; D006801:Humans; D010636:Phenols / Q000494:pharmacology; D059808:Polyphenols
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D016166:Free Radical Scavengers; D010636:Phenols; D059808:Polyphenols