198990-10-2Relevant articles and documents
Design, synthesis, and biological evaluation of 5-aminotetrahydroquinoline-based LSD1 inhibitors acting on Asp375
Yan, Jiangkun,Gu, Yanting,Sun, Yixiang,Zhang, Ziheng,Zhang, Xiangyu,Wang, Xinran,Wu, Tianxiao,Zhao, Dongmei,Cheng, Maosheng
, (2021/05/17)
The abnormal expression of lysine-specific histone demethylase 1 (LSD1) is associated with different cancer types, and LSD1?inhibitory activity seems to have high therapeutic potential in cancer treatment. Here, we report the design, synthesis, and biochemical evaluation of novel 5-aminotetrahydroquinoline-based LSD1 inhibitors. Among them, compounds A6, A8, B1–B5, and C4 showed preferable inhibitory effects on LSD1, with IC50 = 0.19–0.82 μM. Several potent compounds were selected to evaluate their antiproliferative activity on A549 cells and MCF-7 cells with a high expression of LSD1. The potential binding modes of the compounds were revealed through molecular docking to rationalize the potency of compounds toward LSD1. Our data recognized that the 5-aminotetrahydroquinoline scaffold may serve as a starting point for developing potent LSD1 inhibitors for cancer therapy.
Design and synthesis of the first generation of dithiolane thiazolidinedione- and phenylacetic acid-based PPARγ agonists
Chittiboyina, Amar G.,Venkatraman, Meenakshi S.,Mizuno, Cassia S.,Desai, Prashant V.,Patny, Akshay,Benson, Stephen C.,Ho, Christopher I.,Kurtz, Theodore W.,Pershadsingh, Harrihar A.,Avery, Mitchell A.
, p. 4072 - 4084 (2007/10/03)
A series of novel derivatives of potent antioxidant vitamin, α-lipoic acid, and related analogues were designed, synthesized, and evaluated for their PPARγ agonist activities. Compounds 9a and the water soluble analogue 11e were found to be potent PPARγ agonists. Compound 9a appeared to have a significant role in improving insulin sensitivity and reducing triglyceride levels in fa/fa rats as well as inhibited proliferation of a variety of normal and neoplastic cultured human cell types. These novel compounds may prove efficacious not only in the treatment of Type 2 diabetes, but also atherosclerosis, prevention of vascular restenosis, and inflammatory skin diseases.
Solid-phase synthesis of hybrid thiazolidinedione-fatty acid PPARγ ligands
Tomkinson, Nicholas C. O.,Sefler, Andrea M.,Plunket, Kelli D.,Blanchard, Steven G.,Parks, Derek J.,Willson, Timothy M.
, p. 2491 - 2496 (2007/10/03)
A library of thiazolidinedione-fatty acid hybrid molecules was designed to probe the relationship between natural and synthetic PPAR ligands. Solid-phase synthesis of the library led to the identification of several high affinity PPARYγ ligands.
