Résumé
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons. ALS patients develop progressive muscle atrophy, muscle weak and paralysis, finally died of respiratory failure. ALS is characterized by fast aggression and high mortality. What' s more, the disease is highly heterogeneous with unclear pathogenesis and lacks effective drugs for therapy. In this review, we summarize the main pathological mechanisms and the current drugs under development for ALS, which may provide a reference for the drug discovery in the future.
Résumé
Alzheimer's disease (AD) is the most common neurodegenerative disease that causes dementia among elderly people. The pathogenesis of AD is still unclear, and currently approved drugs only provide symptomatic benefits and do not prevent or delay progressive neurodegeneration. Meanwhile, potential drugs in development are facing great challenges in clinical translation. Therefore, finding effective treatment for the unmet clinical needs of AD is of great economic value and social significance. In this review, we will summarize the current models and pharmacodynamics evaluation methods of anti-AD drug based on the recent studies at home and abroad, and provide reference for drug development in AD at nonclinical stage.
Résumé
Alpha7 nicotinic acetylcholine receptor (α7 nAChR) is a ligand-gated ion channel critical for cognition, learning and memory. Deficiency of neuronal α7 nAChR has been implicated in the cognitive deficits and neuropsychiatric disorders. Chemical activation of α7 nAChR improves neurological functions in animal models. In this study, we designed and synthesized a series of indolizine derivatives with various substitutions at different positions on the scaffold, and investigated their structure-activity relationships (SAR). All compounds were screened and evaluated for their agonist activity using the two-electrode voltage clamp recording system in Xenopus oocytes expressing human α7 nAChR. Compound 16c carrying 6-methylindolizine moiety activates α7 nAChR with EC50 at 1.60±0.19 μmol·L-1 and maximum effect (Emax) of 69.0%±2.8% compared with 3 mmol·L-1 ACh. Compound 17b with 8-cyclopropyl substitution shows an increased Emax of 81.1%±9.3% with EC50 at 2.74±0.74 μmol·L-1. The SAR of the series shows that introducing the small hydrophobic groups at 6- or 8- position can improve both potency and maximum effect.
Résumé
<p><b>OBJECTIVE</b>To study the isoflavonoid constituents of the roots of Astragalus membranaceus var. mongholicus.</p><p><b>METHOD</b>Such column chromatography methods as HPD-100 macroporous adsorption resin, silica gel, polyamide and Sephadex LH-20 gel were used for seperating and purifying isoflavonoids, and their structures were identified on the basis of spectral data.</p><p><b>RESULT</b>Fourteen compounds were separated and identified as: formononetin (1), ononin (2) calycosin (3), calycosin-7-O-beta-3-D-glucopyranoside (4), (6aR, 11aR)-3-hydroxy-9,10-dimethoxypterocarpan (5), (6aR, 11aR)-3-hydroxy-9,10-dimethoxypterocarpan-3-O-beta-D-glucopyranoside (6), (3R) -7,2'-dihydroxy-3', 4'-dimethoxyisoflavan (7), (3R) -7, 2'-dihydroxy-3', 4'-dimethoxyisoflavan-7-O-beta-D-glucopyranoside (8), 6"-O-acetyl-ononin (9), 6"-O-acetyl-(3R) -7, 2'-dihydroxy-3', 4'-dimethoxyisoflavan-7-O-beta-D-glucopyranoside (10), 6"-O-acetyl-(6aR, 11aR)-3-hydroxy-9, 10-dimethoxypterocarpan-3-O-beta-D-glucopyranoside (11), pratensein (12), sissotrin (13) and 5,7,4'-trihydroxy-3'-methoxyisoflavone (14).</p><p><b>CONCLUSION</b>Compound 10 was a new compound. Compounds 9, 11, 13,14 were separated from A. membranaceus var. mongholicus for the first time.</p>