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A 15‐kDa lectin, termed SeviL, was isolated from Mytilisepta virgata (purplish bifurcate mussel). SeviL forms a noncovalent dimer that binds strongly to ganglio‐series GM1b oligosaccharide (Neu5Acɑ2‐3Galβ1‐3GalNAcβ1‐4Galβ1‐4Glc) and its precursor, asialo‐GM1 (Galβ1‐3GalNAcβ1‐4Galβ1‐4Glc). SeviL also interacts weakly with the glycan moiety of SSEA‐4 hexaose (Neu5Acα2‐3Galβ1‐3GalNAcβ1‐3Galα1‐4Galβ1‐4Glc). A partial protein sequence of the lectin was determined by mass spectrometry, and the complete sequence was identified from transcriptomic analysis. SeviL, consisting of 129 amino acids, was classified as an R(icin B)‐type lectin, based on the presence of the QxW motif characteristic of this fold. SeviL mRNA is highly expressed in gills and, in particular, mantle rim tissues. Orthologue sequences were identified in other species of the family Mytilidae, including Mytilus galloprovincialis, from which lectin MytiLec‐1 was isolated and characterized in our previous studies. Thus, mytilid species contain lectins belonging to at least two distinct families (R‐type lectins and mytilectins) that have a common β‐trefoil fold structure but differing glycan‐binding specificities. SeviL displayed notable cytotoxic (apoptotic) effects against various cultured cell lines (human breast, ovarian, and colonic cancer; dog kidney) that possess asialo‐GM1 oligosaccharide at the cell surface. This cytotoxic effect was inhibited by the presence of anti‐asialo‐GM1 oligosaccharide antibodies. With HeLa ovarian cancer cells, SeviL showed dose‐ and time‐dependent activation of kinase MKK3/6, p38 MAPK, and caspase‐3/9. The transduction pathways activated by SeviL via the glycosphingolipid oligosaccharide were triggered apoptosis. Database: Nucleotide sequence data have been deposited in the GenBank database under accession numbers MK434191, MK434192, MK434193, MK434194, MK434195, MK434196, MK434197, MK434198, MK434199, MK434200, and MK434201. [ABSTRACT FROM AUTHOR]

We previously proposed a novel QSAR (quantitative structure–activityrelationship) procedure called LERE (linear expression by representativeenergy terms)-QSAR involving molecular calculations such as an abinitio fragment molecular orbital ones. In the present work, we appliedLERE-QSAR to complex formation of matrix metalloproteinase-9 (MMP-9)with a series of substituted biphenylsulfonamides. The results showsthat the overall free-energy change accompanying complex formationis due to predominantly the contribution from the electrostatic interactionwith the zinc atom in the active site of MMP-9. Carbonic anhydrase(CA) belongs to the zinc-containing protease family. In contrast tothe current case of MMP-9, the overall free-energy change during complexformation of CA with a series of benzenesulfonamides is due to thecontributions from the solvation and dissociation free-energy changes,as previously reported. Comparison of the two sets of results indicatesquantitative differences in the relative contributions of free-energycomponents to the overall free-energy change between the two datasets, corresponding with those in the respective classical QSAR equations.The LERE-QSAR procedure was demonstrated to quantitatively revealdifferences in the binding mechanisms between the two cases involvingsimilar but different zinc-containing proteins at the electronic andatomic levels. [ABSTRACT FROM AUTHOR]

Two new pyrrole alkaloids methyl- E -mangolamide (1) and methyl- Z -mangolamide (2), four new megastigmane glycosides nandinamegastigmanes I–IV (3 – 6), and eight known compounds (7 – 14) were isolated from the methanol extract of the fruits of Nandina domestica. The structures of the new compounds were elucidated based on chemical and spectroscopic evidence. The absolute stereochemistry of nandinamegastigmane I (3) was established upon comparing the experimental and predicted electronic circular dichroism (ECD) data. Among the isolated compounds, 1 and 2 showed cell death-inducing activity on the Adriamycin-treated HeLa cells. In addition, one of the mechanisms for cell death-inducing activity of 1 and 2 was suggested as inhibition of P-glycoprotein. [Display omitted] • From Nandina domestica , two new pyrrole alkaloids were isolated. • Four new megastigmane glycosides, nandinamegastigmanes I–IV were isolated. • The absolute configuration of nandinamegastigmane I was established by ECD calculation. • Pyrrole alkaloids induced cell death on the Adriamycin-treated HeLa cells. • The mechanism for above activity was suggested as inhibition of P-glycoprotein. [ABSTRACT FROM AUTHOR]

We isolated the new sesquiterpenes, valerianaterpenes IV and V, and the new lignans valerianalignans I-III from the methanol extracts of the rhizomes and roots of Valeriana fauriei and elucidated their structures based on chemical and spectroscopic findings. The absolute configuration of valerianaterpene IV and valerianalignans I-III were established by comparing experimental and predicted electronic circular dichroism (ECD) data. Among the isolated compounds, valerianalignans I and II exerted anti-proliferative activity against human astrocytoma cells (U-251 MG) and their cancer stem cells (U-251 MG CSCs). Interestingly, valerianalignans I and II notably exerted anti-proliferative activities at lower concentrations against CSCs than non-CSCs, and the absolute configurations of these compounds affected their activities.

Sulfur-containing compounds, such as cyclic compounds with a vinyl sulfane structure, exhibit a wide range of biological activities including anticancer activity. Therefore, the development of efficient strategies to synthesize such compounds is a remarkable achievement. We have developed a unique approach for the rapid and modular preparation of nature-inspired cyclic and acyclic sulfur-containing compounds using thioacrolein, a naturally occurring chemically unstable intermediate. We constructed thiopyranone derivatives through the regioselective sequential double Diels-Alder reaction of thioacrolein produced by allicin, a major component in garlic, and two molecules of silyl enol ether as the diene partner. The cytotoxicity toward cancer stem cells of the thiopyranones was equal to or higher than that of ( Z )-ajoene (positive control) derived from garlic, and the thiopyranones had higher chemical stability than ( Z )-ajoene.