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.
Highlights
Ipomotaosides are resin glycosides derived from the aerial parts of Ipomea batatas
This intermediate moves to the peroxidase active site to be reduced to PGH2, which is converted into other prostaglandins and thromboxanes responsible for mediating the inflammatory process [6], so the inhibition of both COXs by ipomotaoside A indicates a potential role of these molecules in modulating inflammation
On the basis of the ipomotaosides’ structures, two glycosidic linkages had their conformational behavior were evaluated by metadynamics, in both pyridine and water: α-L-Rha-(1→4)-α-L-Rha and α-L-Rha-(1→2)-β-D-Fuc
Summary
Ipomotaosides are resin glycosides derived from the aerial parts of Ipomea batatas. These resin glycosides are separated in four different structures, named ipomotaosides A (1), B (2), C (3), and D (4) [1]. Recent results demonstrated that ipomotaoside A from I. batatas is capable of inhibiting cyclooxygenases (COX) 1 and 2 [1] These enzymes are committed in prostanoid biosynthesis, converting arachidonic acid (AA) and O2 to prostaglandin endoperoxide PGH2 in two different active sites, cyclooxygenase and peroxidase [6]. The conformational ensemble in pyridine was used as reference for spectroscopic validation, and the so-obtained most abundant conformation of ipomotaoside A in aqueous solution was submitted to docking studies to provide insights into its inhibitory activity against COXs. The strategy employed for conformational characterization of ipomotaosides was previously described [11] and validated against NMR data for compounds such as saponins [12], exopolysaccharides [13], galactans and fucans [14], and a series of glycoproteins and glycopeptides [11,15], based on building glycan chains from most abundant conformational states in solution, as determined by MD simulations. The built molecules were submitted to additional simulations in order to account to potential inter-residue interactions and, conformational effects
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
