title: Natural products in medicine: transformational outcome of synthetic chemistry.
abstract: This review brings to the forefront key synthetic modifications on natural products (NPs) that have yielded successful drugs. The emphasis is placed on the power of targeted chemical transformations in enhancing the therapeutic value of NPs through optimization of pharmacokinetics, stability, potency, and/or selectivity. Multiple classes of NPs such as macrolides, opioids, steroids, and β-lactams used to treat a variety of conditions such as cancers, infections, inflammation are exemplified. Molecular modeling or X-ray structures of NP/protein complexes supporting the observed boost in therapeutic value of the modified NPs are also discussed. Significant advancement in synthetic chemistry, in structure determination, and in the understanding of factors controlling pharmacokinetics can now better position drug discovery teams to undertake NPs as valuable leads. We hope that the beneficial NPs synthetic modifications outlined here will reignite medicinal chemists' interest in NPs and their derivatives.
authors.affiliation: Vertex Pharmaceuticals (Canada), Inc. , 275 Armand-Frappier, Laval, Québec H7V 4A7, Canada.
authors.forename: Janek
authors.initials: J
authors.lastname: Szychowski
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Truchon
authors.forename: Youssef L
authors.initials: YL
authors.lastname: Bennani
mesh_terms: D000701:Analgesics, Opioid / Q000737:chemistry; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry; D001688:Biological Products / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D018360:Crystallography, X-Ray; D015195:Drug Design; D055808:Drug Discovery; D006801:Humans; D018942:Macrolides / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D010455:Peptides / Q000737:chemistry; D012995:Solubility; D012997:Solvents; D013256:Steroids / Q000737:chemistry; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000737:chemistry
chemical_list: D000701:Analgesics, Opioid; D000900:Anti-Bacterial Agents; D001688:Biological Products; D018942:Macrolides; D010455:Peptides; D012997:Solvents; D013256:Steroids; D043823:Taxoids