159846-14-7Relevant articles and documents
New Spisulosine Derivative promotes robust autophagic response to cancer cells
Chaturvedi, Priyank,Datta, Dipak,Ganesher, Asha,Meena, Sanjeev,Mitra, Kalyan,Panda, Gautam,Sahai, Rohit
, (2020/01/13)
Therapy resistance by evasion of apoptosis is one of the hallmarks of human cancer. Therefore, restoration of cell death by non-apoptotic mechanisms is critical to successfully overcome therapy resistance in cancer. By rational drug design approach, here we try to provide evidence that subtle changes in the chemical structure of spisulosine completely switched its cytotoxic function from apoptosis to autophagy. Our most potent molecule (26b) in a series of 16 synthesized derivatives showed robust autophagic cell death in diverse cancer cells sparing normal counterpart. Compound 26b mediated lethal autophagy induction was confirmed by formation of characteristic autophagic vacuoles, LC3 puncta formation, upregulation of signature autophagy markers like Beclin and Atg family proteins. Altogether, we have detected novel autophagy inducer small molecule which can be tested further for drug discovery research.
CERAMIDE DERIVATIVE HAVING SMS2 INHIBITORY ACTIVITY
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Paragraph 0071, (2017/09/02)
PROBLEM TO BE SOLVED: To provide a ceramide derivative having excellent SMS2 inhibitory activity, preferably, a ceramide derivative having high SMS2 selectivity. SOLUTION: The present invention provides a compound represented by formula (I) or a pharmaceu
(+)-Saxitoxin: A first and second generation stereoselective synthesis
Fleming, James J.,McReynolds, Matthew D.,Du Bois
, p. 9964 - 9975 (2008/03/17)
A stereoselective synthesis of the bis-guanidinium toxin (+)-saxitoxin (STX), the agent infamously associated with red tides and paralytic shellfish poisoning, is described. Our approach to this unique natural product advances through an unusual nine-membered ring guanidine intermediate 39 en route to the tricyclic skeleton that defines STX. The effectiveness of this strategy is notable, as only four steps are needed to transform 39 into the target molecule, including a four-electron alkene oxidation catalyzed by OsCl3. Construction of the critical monocyclic guanidine has been achieved through two channels, the first of which makes use of Rh-catalyzed C-H amination and highlights a novel class of heterocyclic N,O-acetals as iminium ion equivalents for crafting functionalized amines. A second route to 39 relies on a stereoselective acetylide dianion addition to a serine-based nitrone, thereby facilitating the preparation of STX in just 14 linear steps from commercial material.