title: Rational selection of structurally diverse natural product scaffolds with favorable ADME properties for drug discovery.
abstract: Natural product analogs are significant sources for therapeutic agents. To capitalize efficiently on the effective features of naturally occurring substances, a natural product-based library production platform has been devised at Aurigene for drug lead discovery. This approach combines the attractive biological and physicochemical properties of natural product scaffolds, provided by eons of natural selection, with the chemical diversity available from parallel synthetic methods. Virtual property analysis, using computational methods described here, guides the selection of a set of natural product scaffolds that are both structurally diverse and likely to have favorable pharmacokinetic properties. The experimental characterization of several in vitro ADME properties of twenty of these scaffolds, and of a small set of designed congeners based upon one scaffold, is also described. These data confirm that most of the scaffolds and the designed library members have properties favorable to their utilization for creating libraries of lead-like molecules.
authors.affiliation: Aurigene Discovery Technologies, Ltd., Electronic City Phase 2, Hosur Road, Bangalore-562158, India.
authors.forename: D S
authors.initials: DS
authors.lastname: Samiulla
authors.forename: V V
authors.initials: VV
authors.lastname: Vaidyanathan
authors.forename: P C
authors.initials: PC
authors.lastname: Arun
authors.forename: G
authors.initials: G
authors.lastname: Balan
authors.forename: M
authors.initials: M
authors.lastname: Blaze
authors.forename: S
authors.initials: S
authors.lastname: Bondre
authors.forename: G
authors.initials: G
authors.lastname: Chandrasekhar
authors.forename: A
authors.initials: A
authors.lastname: Gadakh
authors.forename: R
authors.initials: R
authors.lastname: Kumar
authors.forename: G
authors.initials: G
authors.lastname: Kharvi
authors.forename: H O
authors.initials: HO
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: J A
authors.initials: JA
authors.lastname: Malikayil
authors.forename: M
authors.initials: M
authors.lastname: Moger
authors.forename: M K
authors.initials: MK
authors.lastname: Mone
authors.forename: P
authors.initials: P
authors.lastname: Nagarjuna
authors.forename: C
authors.initials: C
authors.lastname: Ogbu
authors.forename: D
authors.initials: D
authors.lastname: Pendhalkar
authors.forename: A V S Raja
authors.initials: AV
authors.lastname: Rao
authors.forename: G Venkateshwar
authors.initials: GV
authors.lastname: Rao
authors.forename: V K
authors.initials: VK
authors.lastname: Sarma
authors.forename: S
authors.initials: S
authors.lastname: Shaik
authors.forename: G V R
authors.initials: GV
authors.lastname: Sharma
authors.forename: S
authors.initials: S
authors.lastname: Singh
authors.forename: C
authors.initials: C
authors.lastname: Sreedhar
authors.forename: R
authors.initials: R
authors.lastname: Sonawane
authors.forename: U
authors.initials: U
authors.lastname: Timmanna
authors.forename: L W
authors.initials: LW
authors.lastname: Hardy
mesh_terms: D000470:Alkaloids / Q000737:chemistry*; D001685:Biological Factors / Q000737:chemistry*; D065607:Cytochrome P-450 Enzyme Inhibitors; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis*; D010936:Plant Extracts / Q000737:chemistry*; D012995:Solubility
chemical_list: D000470:Alkaloids; D001685:Biological Factors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D004364:Pharmaceutical Preparations; D010936:Plant Extracts; C052548:vasicinone