Conformational characterization of ipomotaosides and their recognition by COX-1 and 2

TY - JOUR

T1 - Conformational characterization of ipomotaosides and their recognition by COX-1 and 2

AU - Arantes, Pablo R.

AU - Sachett, Liana G.

AU - Graebin, Cedric S.

AU - Verli, Hugo

PY - 2014/4/24

Y1 - 2014/4/24

N2 - 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.

AB - 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.

KW - COX

KW - Disaccharides

KW - Docking

KW - Inflammatory process

KW - Ipomotaosides

KW - Molecular dynamics

KW - Resin glycosides

UR - https://www.scopus.com/pages/publications/84899582260

U2 - 10.3390/molecules19045421

DO - 10.3390/molecules19045421

M3 - Article

C2 - 24879586

AN - SCOPUS:84899582260

SN - 1420-3049

VL - 19

SP - 5421

EP - 5433

JO - Molecules

JF - Molecules

IS - 4

ER -