title: Conformational characterization of ipomotaosides and their recognition by COX-1 and 2.
abstract: The aerial parts of Ipomoea batatas are described herein to produce four new resin glycosides, designated as ipomotaosides A, B, C, and D. Ipomotaoside A was found to present inhibitory activity on both cyclooxygenases. However, the conformational elucidation of these molecules may be difficult due to their high flexibility. In this context, the current work presents a conformational characterization of ipomotaosides A-D in aqueous and nonaqueous solvents. The employed protocol includes metadynamics evaluation and unrestrained molecular dynamics simulations (MD). The obtained data provided structural models for the ipomotaosides in good agreement with previous ROESY distances measured in pyridine. Accordingly, the most abundant conformation of ipomotaoside A in solution was employed in flexible docking studies, providing a structural basis for the compound's inhibition of COX enzymes. The so-obtained complex supports resin glycosides' role as original scaffolds for future studies, aiming at structural optimization and development of potential new anti-inflammatory agents.
authors.affiliation: Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves 9500, CP 15005, Porto Alegre, RS 91500-970, Brazil. pabloarantes@cbiot.ufrgs.br.
authors.forename: Pablo R
authors.initials: PR
authors.lastname: Arantes
authors.affiliation: Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves 9500, CP 15005, Porto Alegre, RS 91500-970, Brazil. lianasachett@cbiot.ufrgs.br.
authors.forename: Liana G
authors.initials: LG
authors.lastname: Sachett
authors.affiliation: Departamento de Química, Instituto de Ciências Exatas, Universidade Federal Rural do Rio de Janeiro, Cidade Universitária, Seropedica, RJ 23897-000, Brazil. cedric@ufrrj.br.
authors.forename: Cedric S
authors.initials: CS
authors.lastname: Graebin
authors.affiliation: Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Avenida Bento Gonçalves 9500, CP 15005, Porto Alegre, RS 91500-970, Brazil. hverli@cbiot.ufrgs.br.
authors.forename: Hugo
authors.initials: H
authors.lastname: Verli
mesh_terms: D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D051545:Cyclooxygenase 1 / Q000737:chemistry*; D051546:Cyclooxygenase 2 / Q000737:chemistry*; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry*; D006027:Glycosides / Q000737:chemistry*; D027723:Ipomoea batatas / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D010936:Plant Extracts / Q000737:chemistry; D011485:Protein Binding; D012116:Resins, Plant / Q000737:chemistry
chemical_list: D016861:Cyclooxygenase Inhibitors; D006027:Glycosides; D010936:Plant Extracts; D012116:Resins, Plant; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2