Ized by means of the pore formation (by cucumariosides A1 (40) and A8 (44)), preceded by bonding with the glycosides with membrane sphingomyelin, phospholipids, and cholesterol. Noncovalent intermolecular interactions inside multimolecular membrane complexes and their stoichiometry differed for 40 and 44. The second mechanism was realized by cucumarioside A2 (59) by means of the formation of phospholipid and cholesterol clusters inside the outer and inner membrane leaflets, correspondingly. Noticeably, the glycoside/phospholipid interactions were much more favorable in comparison with the glycoside/cholesterol interactions, however the glycoside possessed an agglomerating D-Fructose-6-phosphate disodium salt supplier action towards the cholesterol molecules in the inner membrane leaflet. In silico simulations in the interactions of cucumarioside A7 (45) with model membrane demonstrated only slight interactions with phospholipid polar heads and the absence of glycoside/cholesterol interactions. This reality correlated properly with quite low experimental hemolytic activity of this substance. The observed peculiarities of membranotropic action are in very good agreement with the corresponding experimental data on hemolytic activity of your investigated compounds in vitro. Keywords and phrases: triterpene glycosides; sea cucumber; membranolytic action; hemolytic; Tianeptine sodium salt custom synthesis cytotoxic activity; molecular dynamic simulationPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.1. Introduction The majority of triterpene glycosides from sea cucumbers possess powerful hemolytic and cytotoxic actions against distinct cells, such as cancer cells [1]. Even so, the mechanism of their membranolytic action isn’t yet fully understood in the molecular level, especially in relation to the structural diversity of these compounds. Some trends of SAR of sea cucumber glycosides happen to be discussed [5,6], however the molecular interactions of distinct functional groups together with the components of biomembranes which influence the membranotropic action with the glycosides stay unexplored. The broad spectrum of bioactivity of sea cucumber triterpene glycosides derives from their ability to interact together with the lipid constituents on the membrane bilayer, changing theCopyright: 2021 by the authors. Licensee MDPI, Basel, Switzerland. This short article is definitely an open access write-up distributed below the terms and conditions of the Inventive Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ four.0/).Mar. Drugs 2021, 19, 604. https://doi.org/10.3390/mdhttps://www.mdpi.com/journal/marinedrugsMar. Drugs 2021, 19,2 offunctional properties on the plasmatic membrane. Sterols are very crucial structural components influencing the properties and functions of eukaryotic cell membranes. The selective bonding to the sterols with the cell membranes underlines the molecular mechanisms of action of a lot of all-natural toxins, such as triterpene glycosides with the sea cucumbers. The formation of complexes with five,6-unsaturated sterols of target cell membranes is the basis of their biological activity which includes ichthyotoxic action that may protect sea cucumbers against fish predation. In fact, some experimental data indicated the interaction in the aglycone portion of the glycosides with cholesterol [7,8]. The saturation of ascites cell membranes with cholesterol increased the cytotoxicity from the sea cucumber glycosides [9]. This complexing reaction of both the animal and plant saponins leads to the formation of pores, the perm.
