The Synthesis and Fungicidal Activity of 2-Substituted 1-Azol-1-ylmethyl-6-arylidenecyclohexanols

A number of substituted 2,2-dimethyl-6-arylidene-1-triazol-1-ylmethylcyclohexanols and 2,2-dimethyl-6-arylidene-1-imidazol-1-ylmethylcyclohexanols were prepared from 2-methylcyclohexanone in four steps: Claisen–Schmidt condensation with substituted benzaldehydes, methylation of the resulting 2-methyl-6-benzylidenecyclohexanones, conversion to the oxiranes by interaction with dimethylsulfonium methylide and reaction of the oxiranes with triazole or imidazole. The compounds obtained were tested for antifungal activity against five phytopathogenic fungi of different taxonomic classes. EC₅₀ values were determined for all compounds. Structure–activity relationships are discussed in broad terms. Some of triazolymethyl-substituted cyclohexanols obtained are more active than triadimenol. © 1997 SCI.     

Structure-Activity Relationships of Holothuroid’s Triterpene Glycosides and Some In Silico Insights Obtained by Molecular Dynamics Study on the Mechanisms of Their Membranolytic Action

The article describes the structure-activity relationships (SAR) for a broad series of sea cucumber glycosides on different tumor cell lines and erythrocytes, and an in silico modulation of the interaction of selected glycosides from the sea cucumber Eupentacta fraudatrix with model erythrocyte membranes using full-atom molecular dynamics (MD) simulations. The in silico approach revealed that the glycosides bound to the membrane surface mainly through hydrophobic interactions and hydrogen bonds. The mode of such interactions depends on the aglycone structure, including the side chain structural peculiarities, and varies to a great extent. Two different mechanisms of glycoside/membrane interactions were discovered. The first one was realized through the pore formation (by cucumariosides A₁ (40) and A₈ (44)), preceded by bonding of 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) through the formation of phospholipid and cholesterol clusters in the outer and inner membrane leaflets, correspondingly. Noticeably, the glycoside/phospholipid interactions were more favorable compared to the glycoside/cholesterol interactions, but the glycoside possessed an agglomerating action towards the cholesterol molecules from the inner membrane leaflet. In silico simulations of 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 fact correlated well with very low experimental hemolytic activity of this substance. The observed peculiarities of membranotropic action are in good agreement with the corresponding experimental data on hemolytic activity of the investigated compounds in vitro.     

LTSER platforms as a place-based transdisciplinary research infrastructure: learning landscape approach through evaluation

Landscape Ecology - Place-based transdisciplinary research involves multiple academic disciplines and non-academic actors. Long-Term Socio-Ecological Research (LTSER) platform is one concept with ~...     

Antiviral Potential of Sea Urchin Aminated Spinochromes against Herpes Simplex Virus Type 1

Herpes simplex virus type 1 (HSV-1) is one of the most prevalent pathogens worldwide requiring the search for new candidates for the creation of antiherpetic drugs. The ability of sea urchin spinochromes—echinochrome A (EchA) and its aminated analogues, echinamines A (EamA) and B (EamB)—to inhibit different stages of HSV-1 infection in Vero cells and to reduce the virus-induced production of reactive oxygen species (ROS) was studied. We found that spinochromes exhibited maximum antiviral activity when HSV-1 was pretreated with these compounds, which indicated the direct effect of spinochromes on HSV-1 particles. EamB and EamA both showed the highest virucidal activity by inhibiting the HSV-1 plaque formation, with a selectivity index (SI) of 80.6 and 50.3, respectively, and a reduction in HSV-1 attachment to cells (SI of 8.5 and 5.8, respectively). EamA and EamB considerably suppressed the early induction of ROS due to the virus infection. The ability of the tested compounds to directly bind to the surface glycoprotein, gD, of HSV-1 was established in silico. The dock score of EchA, EamA, and EamB was −4.75, −5.09, and −5.19 kcal/mol, respectively, which correlated with the SI of the virucidal action of these compounds and explained their ability to suppress the attachment and penetration of the virus into the cells.     

Pikeperch (Sander lucioperca) spermatozoa motility and volume regulation under different osmotic and ionic conditions

Fish Physiology and Biochemistry - Pikeperch (Sander lucioperca) is a highly profitable commercial species whose economic value has greatly increased in the last decade. As in other species, the...