Search results for " alkaloids"
showing 10 items of 84 documents
Improved Expression of His6-Tagged Strictosidine Synthase cDNA for Chemo-Enzymatic Alkaloid Diversification
2010
Strictosidine synthase (STR1) catalyzes the stereoselective formation of 3alpha(S)-strictosidine from tryptamine and secologanin. Strictosidine is the key intermediate in the biosynthesis of 2,000 plant monoterpenoid indole alkaloids, and it is a key precursor of enzyme-mediated synthesis of alkaloids. An improved expression system is described which leads to optimized His(6)-STR1 synthesis in Escherichia coli. Optimal production of STR1 was achieved by determining the impact of co-expression of chaperones pG-Tf2 and pG-LJE8. The amount and activity of STR1 was doubled in the presence of chaperone pG-Tf2 alone. His(6)-STR1 immobilized on Ni-NTA can be used for enzymatic synthesis of stricto…
Sonic hedgehog promotes angiogenesis and osteogenesis in a coculture system consisting of primary osteoblasts and outgrowth endothelial cells.
2009
A number of previous studies documented the angiogenic potential of outgrowth endothelial cells in vitro and in vivo and provided evidence that therapeutic success could depend on coculture or coimplantation strategies. Thus, deeper insight into the molecular mechanisms underlying this pro-angiogenic effect of cocultures might provide new translational options for tissue engineering and regenerative medicine. One promising signaling pathway in bone repair involved in neoangiogenesis and bone formation is the sonic hedgehog (Shh) pathway. In this article, we focus on the effect of Shh on the formation of microvessel-like structures and osteoblastic differentiation in cocultures of primary os…
Molecular docking and pharmacogenomics of vinca alkaloids and their monomeric precursors, vindoline and catharanthine.
2011
International audience; Vinblastine and vincristine are dimeric indole alkaloids derived from (formerly: ). Their monomeric precursor molecules are vindoline and catharanthine. While vinblastine and vincristine are well-known mitotic spindle poisons, not much is known about vindoline and catharanthine. Vindoline and catharanthine showed weak cytotoxicity, while vinblastine, vincristine, and the semisynthetic vindesine and vinorelbine revealed high cytotoxicity towards cancer cells. This may reflect a general biological principle of poisonous plants. Highly toxic compounds are not only active towards predators, but also towards plant tissues. Hence, plants need mechanisms to protect themselv…
New 1,2,4-oxadiazole nortopsentin derivatives with cytotoxic activity
2019
New analogs of nortopsentin, a natural 2,4-bis(3&prime
Nuevos fármacos inspirados en Annonáceas
2014
Los metabolitos secundarios activos (MSA) juegan un papel importante en el descubrimiento de nuevos medicamentos. Moléculas naturales con esqueletos complejos, tales como las estatinas aisladas de Aspergillus terreus, o las acetogeninas específicas de la familia Annonaceae, no hubieran podido ser inventadas en ningún laboratorio. Los MSA aislados en Annonaceae, especialmente las acetogeninas y los alcaloides isoquinoleínicos, pueden ser considerados como fuente constante de inspiración para químicos, farmacólogos y para todos los investigadores interesados en el descubrimiento de una nueva familia de medicamentos. Active secondary metabolites (ASM) play a highly significant role in the drug…
Synthesis and Antitumor Activity of New Thiazole Nortopsentin Analogs
2016
New thiazole nortopsentin analogs in which one of the two indole units was replaced by a naphthyl and/or 7-azaindolyl portion, were conveniently synthesized. Among these, three derivatives showed good antiproliferative activity, in particular against MCF7 cell line, with GI50 values in the micromolar range. Their cytotoxic effect on MCF7 cells was further investigated in order to elucidate their mode of action. Results showed that the three compounds act as pro-apoptotic agents inducing a clear shift of viable cells towards early apoptosis, while not exerting necrotic effects. They also caused cell cycle perturbation with significant decrease in the percentage of cells in the G0/G1 and S ph…
Stereoselective Synthesis of the Glycosidase Inhibitor Australine through a One-Pot, Double-Cyclization Strategy
2006
[reaction: see text] A stereocontrolled, convergent synthesis of the alkaloid australine, a glycosidase inhibitor of the pyrrolizidine class, is described. The chiral starting materials were ketone 3, derived from L-erythrulose, and alpha-alkoxy aldehyde 4, prepared from L-malic acid. A key step of the synthesis was the highly stereoselective aldol reaction between 4 and a Z boron enolate derived from 3. Another key step was the one-pot construction of the bicyclic pyrrolizidine system by means of a three-step sequence of SN2 displacements induced by benzylamine on a trimesylate precursor.
Zur C-17-Oxidation von Clavinalkaloiden mit primärer alkoholischer Hydroxylgruppe
1975
Die Oppenauer-Oxidation von 1 mit Cyclohexanon fuhrt zu dem Aldolkondensationsprodukt 4 und der Carbonsaure 3. Analog konnte Lysergsaure (8) in geringer Menge aus 6 gewonnen und im Reaktionsgemisch von 7 nachgewiesen werden. Damit wurden erstmals Clavinalkaloide mit primarer alkoholischer Hydroxylgruppe chemisch zu den entsprechenden Carbonsauren oxidiert. C-17-Oxidation of Clavine Alkaloids with a Primary Alcoholic Hydroxyl Group. 1 is converted by Oppenauer oxidation with cyclohexanone to the aldol condensation product 4 and to the carboxylic acid 3. Lysergic acid (8) was obtained in a small yield by the analogous reaction of 6 and was found in the reaction mixture of 7. Thus clavine alka…
Partialsynthese neuer Ergolinderivate aus Clavinalkoloiden, 5. Mitt. N-1- und N-6-mono- und disubstituierte Festuclavine
1985
Festuclavin (1), 6-Cyano-6-nor-1 (3), 6-Nor-1 (5) und 6-Allyl-6-nor-1 (7) lassen sich in flussigem Ammoniak mit Kalium und dem entsprechenden Iodid in ihre 1-Allyl- und 1-Propyl-Derivate uberfuhren. Die Darstellung von 7 aus 5 wird beschrieben. Partial Syntheses of New Ergoline Derivatives from Clavine Alkaloids, V: Festuclavines Mono- and Disubstituted at N-1 and N-6 Festuclavine (1), 6-cyano-6-nor-1 (3), 6-nor-1 (5) and 6-allyl-6-nor-1 (7) were converted to their 1-allyl- and 1-propyl derivatives with potassium and the corresponding iodide in ammonia. The preparation of 7 from 5 is described.
The hedgehog receptor patched is involved in cholesterol transport.
2011
International audience; BACKGROUND: Sonic hedgehog (Shh) signaling plays a crucial role in growth and patterning during embryonic development, and also in stem cell maintenance and tissue regeneration in adults. Aberrant Shh pathway activation is involved in the development of many tumors, and one of the most affected Shh signaling steps found in these tumors is the regulation of the signaling receptor Smoothened by the Shh receptor Patched. In the present work, we investigated Patched activity and the mechanism by which Patched inhibits Smoothened. METHODOLOGY/PRINCIPAL FINDINGS: Using the well-known Shh-responding cell line of mouse fibroblasts NIH 3T3, we first observed that enhancement …