Conjugating oligosaccharides to proteins by squaric acid diester chemistry: rapid monitoring of the progress of conjugation, and recovery of the unused ligand

Samples that are periodically withdrawn from the mixture of a conjugation reaction can be analyzed on a picomolar scale without any work-up or pre-purification using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) in combination with the ProteinChip^® System. The technique provides rapid information about the increasing molecular mass of the glycoconjugate formed, thereby allowing termination of the process when the desired incorporation of the ligand onto the carrier protein is achieved. The excess oligosaccharide used at the onset of conjugation can be recovered and used in preparation of a similar neoglycoconjugate. The overall economy of conjugations, which often involve labor-intensive linker-equipped oligosaccharides, can be markedly increased in this way.     

Design,synthesis and antitumour and anti-angiogenesis evaluation of 22 moscatilin derivatives

Two series of moscatilin derivatives were designed, synthesized and evaluated as anti-tumor and anti-angiogenesis agents. Most of these compounds showed moderate-to-obvious cytotoxicity against five cancer cell lines (A549, HepG2, MDA-MB-231, MKN-45, HCT116). Among these cell lines, compounds had obvious effects on HCT116. Especially for 8Ae, the IC₅₀ was low to 0.25 μM. 8Ae can inhibit the viability and induce the apoptosis of HCT116 cells but exhibit no cytotoxic activity in noncancerous NCM460 colon cells. 8Ae can also arrest the G2/M cell cycle in HCT116 cells by inhibiting the α-tubulin expression. Zebrafish bioassay-guided screen showed the 22 moscatilin derivatives had potent anti-angiogenic activities and compound 8Ae had better activities than positive compound. Molecular docking indicated 8Ae interacted with tubulin at the affinity of −7.2 Kcal/mol. In conclusion, compound 8Ae was a potential antitumor and anti-angiogenesis candidate for further development.     

New germacranolides,guaianolides and rearranged Guaianolides from Lasiolaena santosii

The aerial parts of L. santosii afforded three new diterpenes, a phenylpropanol, three eudesmane derivatives, three germacranolides, seventeen guaianolides and four rearranged guaianolides of a, so far, unknown type. Furthermore, several known compounds were isolated. The structures of the new compounds, the separations of which caused difficulties, were elucidated by spectroscopic methods and by some chemical transformations. The chemotaxonomic situation is discussed briefly.     

Essai chimiosystématique sur la tribu des Lotées

A survey of the leaves and flowers of 62 representatives of the tribe Loteae (Leguminosae) showed the presence of several classes of flavonoids: flavonol 7-methyl ethers (rhamnocitrin, rhamnetin), 8-O-substituted flavonols (gossypetin, limocitrin, sexangularetin, corniculatusin), 3′,4′,5′-tri-O-substituted flavonols (myricetin, mearnsetin, syringetin, laricitrin), proanthocyanidins and flavone-C-glycosides. The trisubstitution of the B-ring and the 8-O-substitution of the A-ring allow the definition of a major group including the genera Dorycnium, Bonjeania, Lotus and Tetragonolobus. The presence of proanthocyanidins and 7-O-methylation determine a second group consisting of the genus Anthyllis. Finally, Securigera, on the basis of its flavonoid chemistry, appears to be rather remote from other members of the tribe.     

8-Hydroxypegolettiolide,a sesquiterpene lactone with a new carbon skeleton and further constituents from Pegolettia senegalensis

The investigation of Pegolettia senegalensis afforded several new sesquiterpene lactones, eight cis-6,12-germacra-trans,trans-1(10),4,11-trienolides, five cis-6,12-eudesmanolides, two elemanolides, 8,14-cyclogermacra-1(10),4,7(11)-trien-6,12-olide with a new carbon skeleton, three germacra-1(10),4,11(13)-trien-12-oic acids with ester residues at C-8, 18-hydroxygeranyl nerol, 1,3-dihydroxyoctadecane and a mixture of esters of 3,4-dihydroxy-dihydrocinnamyl alcohol. The structures were elucidated by high field ¹HNMR spectroscopy and some chemical transformations. The C-10 configuration of 6,12-cis-eudesmanolides from Calostephane divaricata and Inula crithmoides most likely has to be corrected. The chemotaxonomic situation of the genus Pegolettia and biogenetic considerations are discussed briefly.     

Cis-4-hydroxypipecolic acid and 2,4-cis-4,5-trans-4,5-dihydroxypipecolic acid from Calliandra

cis-4-Hydroxypipecolic acid and 2,4-cis-4,5-trans-4,5-dihydroxypipecolic acid were isolated from leaves of Calliandra pittieri. A system for resolving the eight imino acids isolated from Calliandra is described.     

Stereoselective binding and activity of oxotremorine analogs at muscarinic receptors in rat brain.

The activities of the enantiomers of BM-5 were examined to measure muscarinic cholinergic selectivity in the central nervous system. Autoradiographic studies assessed the ability of each enantiomer to inhibit the binding of [3H]-(R)-quinuclidinyl benzilate ([3H]-(R)-QNB) to muscarinic receptors in the rat brain. (+)-(R)-BM-5 inhibited [3H]-(R)-QNB binding to rat brain sections at concentrations below 1.0 microM, while 100-fold higher concentrations of (-)-(S)-BM-5 were required for comparable levels of inhibition. Analysis of the autoradiograms indicated that both stereoisomers had a similar distribution of high affinity binding sites. Each enantiomer displayed higher affinity for muscarinic receptors in the superior colliculi and lower affinity for receptors in the cerebral cortex and hippocampus. (+)-(R)-BM-5 and oxotremorine inhibited adenylyl cyclase activity in the cerebral cortex with efficacies comparable to that for acetylcholine. (+)-(R)-BM-5 was 26-fold more potent than (-)-(S)-BM-5 in inhibiting adenylyl cyclase. Oxotremorine-M and carbamylcholine stimulated phosphoinositide turnover in the cerebral cortex. Oxotremorine had lower activity and (+)-(R)-BM-5 was essentially inactive at comparable concentrations. The difference in activity of the two enantiomers indicates a remarkable stereochemical selectivity for muscarinic receptors. The stereoselectivity index is comparable for both the autoradiographic assays (48) and measures of adenylyl cyclase activity (26) in the cerebral cortex.     

A phloroglucinol derivative from the brown alga Zonaria tournefortii

The major lipid component of the brown seaweed Zonaria tournefortii was identified as the acylphlorogluconol (all Z)-2′-icosa-5,8,11,14,17-pentae     

Design,Synthesis, Molecular Docking,and Biological Evaluation of New Emodin Anthraquinone Derivatives as Potential Antitumor Substances

The emodin anthraquinone derivatives are generally used in traditional Chinese medicine due to their various pharmacological activities. In the present study, a series of emodin anthraquinone derivatives have been designed and synthesized, among which 1,3‐dihydroxy‐6,8‐dimethoxyanthracene‐9,10‐dione is a natural compound that has been synthesized for the very first time, and 1,3‐dimethoxy‐5,8‐dimethylanthracene‐9,10‐dione is a compound that has never been reported earlier. Interestingly, while total seven of these compounds showed neuraminidase inhibitory activity in influenza virus with inhibition rate more than 50 %, specific four compounds exhibited significant inhibition of tumor cell proliferation. The further results demonstrate that 1,3‐dimethoxy‐5,8‐dimethylanthracene‐9,10‐dione showed the best anticancer activity among all the synthesized compounds by inducing highest apoptosis rate to HCT116 cancer cells and arresting their G0/G1 cell cycle phase, through elevation of intracellular level of reactive oxygen species (ROS). Moreover, the binding of 1,3‐dimethoxy‐5,8‐dimethylanthracene‐9,10‐dione with BSA protein has thoroughly been investigated. Altogether, this study suggests the neuraminidase inhibitory activity and antitumor potential of the new emodin anthraquinone derivatives.