196497-48-0Relevant articles and documents
Highly diastereoselective total synthesis of the anti-tumoral agent (±)-Spisulosine (ES285) from a Morita-Baylis-Hillman adduct
Amarante, Giovanni W.,Cavallaro, Mayra,Coelho, Fernando
, p. 2597 - 2599 (2010)
We disclose herein a new approach for the highly diastereoselective total synthesis of the anti-tumoral agent (±)-Spisulosine. The synthesis was accomplished in seven steps with an overall yield of 10%. The key step involves the transformation of a Morita-Baylis-Hillman into an acyloin, which was subsequently used as substrate in a highly diastereoselective reductive amination reaction.
Self-assembling nanoparticles of dually hydrophobic prodrugs constructed from camptothecin analogue for cancer therapy
Guan, Huashi,Jiang, Tao,Liu, Jiannan,Liu, Xuemeng,Wang, Xueting,Wu, Guanzhao,Yin, Ruijuan,Yu, Mingming,Yu, Rilei,Zhang, Yixuan
supporting information, (2020/05/25)
Nanomedicines have shown success in cancer therapy in recent years because of their excellent solubility in aqueous solution and drug accumulation through controlled release in tumor tissues, but the preparation of most nanomedicines still requires ionic materials, surfactants or the amphiphilic structure to maintain nanoparticle stability and function. In this study, we developed a couple of novel dually hydrophobic prodrugs (DHPs) by combining two hydrophobic compounds through different linkers and elaborated their self-assembly mechanisms by virtue of computational simulation. Importantly, without using any excipients, FL-2 NPs exhibited significantly prolonged retention in blood circulation and displayed a remarkable anti-tumor effect at very low concentration in vivo. Both DHPs consisted of camptothecin structural analogue(FL118) and a marine natural product (ES-285). Comparative experiments proved that these compounds could quickly form nanoparticles by way of simple preparation and remained relatively stable for long periods in PBS. FL-2 NPs linked with a disulphide bond could rapidly release bioactive FL118 after being triggered by endogenous reductive stimulus to exert anti-cancer effects. Overall, this study provides a new strategy for design of therapeutic nanomedicines consisting of dually hydrophobic molecules for cancer therapy.
Synthesis and identification of unprecedented selective inhibitors of CK1ε
Silveira-Dorta, Gastón,Sousa, Inês J.,Fernandes, Miguel X.,Martín, Victor S.,Padrón, José M.
, p. 308 - 317 (2015/04/27)
A small and structure-biased library of enantiopure anti-β-amino alcohols was prepared in a straightforward manner by a simplified version of the Reetz protocol. Antiproliferative activity testing against a panel of five human solid tumor cell lines gave GI50 values in the range 1-20 μM. The reverse screening by computational methods against 58 proteins involved in cancer pointed to kinases as possible therapeutic target candidates. The experimental determination of the interaction with 456 kinases indicated that the compounds behave as selective CK1ε inhibitors. Our results demonstrate that the lead compound represents the first selective CK1ε inhibitor with proven antiproliferative activity in cancer cell lines.
SELECTIVE INHIBITORS AND ALLOSTERIC ACTIVATORS OF SPHINGOSINE KINASE
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, (2014/08/19)
Sphingosine 1-phosphate (S1P) is involved in hyper-proliferative diseases, such as cancer and vascular remodeling in pulmonary arterial hypertension. Inhibitors of sphingosine kinase 1 and 2 (SK1 and SK2), which catalyze the synthesis of S1P, may be useful anti- proliferative agents. We have synthesized a series of sphingosine-based inhibitors of SK and SK2. Also provided in this invention are compounds that activate SK1 which can be used in diseases such as fibrosis, where intracellular S1P is anti-fibrotic.
