Tivity with the pairs of compounds (Table 1) colochiroside B2 (38) (Figure 7) and magnumoside B1 (eight), also as colochiroside C (36) and magnumoside C3 (14), and differing by the aglycones nuclei (holostane and non-holostane, correspondingly), showed that compounds 36 and 38, which contained the holostane aglycones, were a lot more active, and this really is consistent using the earlier conclusions.Figure 7. Structure of colochiroside B2 (38) from Colochirus robustus.Moreover, the glycosides from the sea cucumber, Cucumaria fallax [42], did not display any activity due to containing uncommon hexa-nor-lanostane aglycones with an eight(9)-double bond and without the need of a lactone. The only glycoside from this series, cucumarioside A3 -2 (39) (Figure 8), that was moderately hemolytic (Table 1) was characterized by hexa-nor-lanostane aglycone, but, as standard for the glycosides of sea cucumbers, getting a 7(eight)-double bond and 9-H configuration, which demonstrates the significance of these Tenidap web structural elements for the membranotropic action from the glycosides.Mar. Drugs 2021, 19,8 ofFigure 8. Structure of cucumarioside A3 -2 from Cucumaria fallax.The influence in the side chain length and character of a lactone (18(20)- or 18(16)-) is nicely illustrated by the comparative analysis of your hemolytic activity on the series of glycosides from E. fraudatrix (cucumariosides A1 (40) and A10 (41) [28,29]; cucumariosides I1 (42) and I4 (43) [43]) (Figure 9), which indicates that the presence of a typical side chain is crucial for the higher membranolytic impact from the glycoside.Figure 9. Structures in the glycosides 403 from Eupentacta fraudatrix.Unexpectedly higher hemolytic activity was displayed by cucumarioside A8 (44) from E. fraudatrix [29] (Figure ten) with one of a kind non-holostane aglycone and without having lactone but with hydroxy-groups at C-18 and C-20, which can be regarded as a biosynthetic precursor of your holostane aglycones. Its robust membranolytic action (Table 1) may be explained by the formation of an intramolecular hydrogen bond between the atoms of aglycone hydroxyls resulting in the spatial structure of your aglycone becoming equivalent to that of ML-SA1 custom synthesis holostane-type aglycones. Noticeably, it truly is of particular interest to check this concern by in silico calculations to clarify the molecular mechanism of membranotropic action of 44.Figure 10. Structure of cucumarioside A8 (44) from Eupentacta fraudatrix.2.1.4. The Influence of Hydroxyl Groups inside the Aglycones Side Chain to Hemolytic Activity in the Glycosides A strong activity-decreasing effect in the hydroxyl groups within the aglycone side chains was revealed for the very first time when the bioactivity of your glycosides from E. fraudatrix was studied [279,43]. In reality, cucumariosides A7 (45), A9 (46), A11 (47), and A14 (48), as well as I3 (49), have been not active against erythrocytes (Table 1) (Figure 11).Mar. Drugs 2021, 19,9 ofFigure 11. Structures on the glycosides 459 from Eupentacta fraudatrix and 50 from Colochirus robustus.Nonetheless, colochirosides B1 (50) (Figure 11) and B2 (38) from C. robustus [24], together with the very same aglycones as cucumariosides A7 (45) and A11 (47), correspondingly, but differing by the third (Xylose) and terminal monosaccharide residues (3-O-MeGlc) as well as the presence of sulfate group at C-4 Xyl1, demonstrated moderate hemolytic activity (Table 1). The activity of typicoside C1 (51) from A. typica [23] too as cladolosides D2 (52) and K2 (53) from C. schmeltzii [40,41], using a 22-OH group within the holostane aglycones, was.
