14358-33-9Relevant articles and documents
Involvement of apoptosis and autophagy in the death of RPMI 8226 multiple myeloma cells by two enantiomeric sigma receptor ligands
Korpis, Katharina,Weber, Frauke,Brune, Stefanie,Wünsch, Bernhard,Bednarski, Patrick J.
, p. 221 - 233 (2014)
Over-expression of σ receptors by many tumor cell lines makes ligands for these receptors attractive as potential chemotherapeutic drugs. Enantiomeric piperazines (S)-4 and (R)-4 were prepared as potential σ-receptor ligands in a chiral pool synthesis starting from (S)- and (R)-aspartate. Both compounds showed high affinities for the σ1 and σ2 receptors. In the human multiple myeloma cell line RPMI 8226, a line expressing high levels of σ receptors, both compounds inhibited cell proliferation with IC50 values in the low μM range. No chiral differentiation between either the σ receptor binding affinity or the cytotoxicity of the two enantiomers was observed. Both compounds induced apoptosis, which was evidenced by nuclear condensation, binding of annexin-V to phosphatidylserine in the outer leaf of the cell membrane, cleavage products of poly(ADP-ribose) polymerase-1 (PARP-1) and caspase-8 as well as the expression of bcl2 family members bax, bad and bid. However, apoptosis appeared to be caspase independent. Increased levels of the phosphorylated form of the microtubule associated protein light chain 3-II (LC3-II), an autophagosome marker, gave evidence that both compounds induced autophagy. However, further data (e.g., treatment with wortmannin) indicate that autophagy is incomplete and not cytoprotective. Lipid peroxidation (LPO) was observed in RPMI 8226 cells treated with the two compounds, and the lipid antioxidant α-tocopherol attenuated LPO. Interestingly, α-tocopherol reduced significantly both apoptosis and autophagy induced by the compounds. These results provide evidence that, by initiating LPO and changes in mitochondrial membrane potential, both compounds induce apoptosis and autophagy in RPMI 8226 cells.
A Synthetic Route to the MT1-MMP Inhibitor Ancorinoside D
Petermichl, Markus,Steinert, Christine,Schobert, Rainer
, p. 730 - 738 (2019/01/23)
A methyl ester of ancorinoside D, a 3-acyltetramic acid metabolite of a sponge Penares sollasi, was synthesised in ten steps starting from a protected β- d -glucopyranosyl-(1→4)- d -galactopyranosyltrichloroacetimidate donor. Its attachment to the left half of the 3-acyl spacer by a Schmidt glycosylation, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation to the uronic acid, introduction of the Z -alkene via Wittig reaction, and functionalisation of the spacer terminus with Meldrum's acid gave a β-keto ester that reacted with dimethyl N -methyl- d -aspartate under neutral conditions to afford a fully protected ancorinoside D as the product of an unusual domino N -acylation-Dieckmann condensation. Global deprotection left a methyl ester of ancorinoside D, which resisted all saponification attempts.
Preparation method of nitrogen-substituted aspartic acid
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Paragraph 0045; 0046; 0047; 0048, (2019/01/24)
The invention discloses a preparation method of nitrogen-substituted aspartic acid, the method comprises the following steps: providing a nitrogen-substituted aspartic acid compound with the structural formula as shown in the specification, wherein R1 is alkyl, and R2 is an amino protecting group; performing deprotection treatment on the nitrogen-substituted aspartic acid compound to obtain the nitrogen-substituted aspartic acid with the structural formula as shown in the specification, and the preparation method disclosed by the invention can be used for reducing the cost of preparing the nitrogen-substituted aspartic acid and enabling the nitrogen-substituted aspartic acid to be suitable for industrial production.
