Ergot alkaloids are secondary metabolites that exist in two configurations, the C-8-R-isomer (R-epimer), and the C-8-S-isomer (S-epimer). Toxic effects of ergot, such as vasoconstriction, have been primarily attributed to the R-epimer bioactivity, as compared to the S-epimer. Recent studies demonstrated potential bioactivity of S-epimers. Therefore, further cost-effective investigations of the S-epimers are needed. The present study investigated the S-epimer - vascular receptor binding relationship. An in silico molecular docking approach, utilizing AutoDock Vina and DockThor, was used to determine if the S-epimer (ergocristinine) binds to vascular receptors and to compare the binding affinity and interactions to the corresponding R-epimer (ergocristine) and a structural analogue (lysergic acid amide). The binding energy (kcal/mol) of ergocristinine was - 9.7 or - 11.0 to the serotonin (5-HT) 2 A receptor and - 8.7 or - 11.4 to the alpha 2 A adrenergic receptor, depending on the software used. A hydrogen bond was formed between ergocristinine and amino acid residues of the 5-HT 2 A and alpha 2 A adrenergic receptor binding sites, with bond lengths of 3.10 Å and 3.28 Å, respectively. Binding affinities and molecular interactions among the ligands to each receptor differed. Different affinities and interactions may relate to differences in the chemical structures. The binding affinities and strong molecular interactions of the S-epimer to vascular receptors may contribute to the observed physiological manifestations that occur after ergot alkaloid exposure. The results of the present study suggest further investigation on the receptor binding of the S-epimers of ergot alkaloids.
Keywords: Affinity; Ergocristine; Ergot alkaloid; Molecular docking; Molecular interactions; Mycotoxin.
© 2023 The Authors.