Novel Soloxolone Amides as Potent Anti-Glioblastoma Candidates: Design, Synthesis, In Silico Analysis and Biological Activities In Vitro and In Vivo was written by Markov, Andrey V.;Ilyina, Anna A.;Salomatina, Oksana V.;Sen’kova, Aleksandra V.;Okhina, Alina A.;Rogachev, Artem D.;Salakhutdinov, Nariman F.;Zenkova, Marina A.. And the article was included in Pharmaceuticals in 2022.COA of Formula: C3H9NO The following contents are mentioned in the article:
The modification of natural or semisynthetic triterpenoids with amines can be explored as a promising strategy for improving their pharmacol. properties. Here, we report the design and synthesis of 11 novel amide derivatives of soloxolone Me (SM), a cyano enone-bearing derivative of 18βH-glycyrrhetinic acid. Anal. of their bioactivities in vitro and in silico revealed their high toxicity against a panel of tumor cells (average IC50(24h) = 3.7 μM) and showed that the formation of amide moieties at the C-30 position of soloxolone did not enhance the cytotoxicity of derivatives toward tumor cells compared to SM, though it can impart an ability to pass across the blood-brain barrier. Further HPLC-MS/MS and mechanistic studies verified significant brain accumulation of hit compound 12 (soloxolone tryptamide) in a murine model and showed its high anti-glioblastoma potential. It was found that 12 induced ROS-dependent and autophagy-independent death of U87 and U118 glioblastoma cells via mitochondrial apoptosis and effectively blocked their clonogenicity, motility and capacity to form vessel-like structures. Further in vivo study demonstrated that i.p. injection of 12 at a dosage of 20 mg/kg effectively inhibited the growth of U87 glioblastoma in a mouse xenograft model, reducing the proliferative potential of the tumor and leading to a depletion of collagen content and normalization of blood vessels in tumor tissue. The obtained results clearly demonstrate that 12 can be considered as a promising leading compound for drug development in glioblastoma treatment. This study involved multiple reactions and reactants, such as 2-Methoxyethylamine (cas: 109-85-3COA of Formula: C3H9NO).
2-Methoxyethylamine (cas: 109-85-3) belongs to ethers. Carboxylic acid esters of low molecular weight are colourless, volatile liquids with pleasant odours, slightly soluble in water. Cyclic esters are called lactones, regardless of whether they are derived from an organic or inorganic acid. One example of an organic lactone is γ-valerolactone.COA of Formula: C3H9NO
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem