(S)-Trolox, an analogue of vitamin E, substitutes the phytyl chain with a carboxyl group. This compound serves as a model substance in structural studies and as a standard for assessing antioxidant activity. Moreover, (S)-Trolox exhibits potent and specific neuroprotective and antioxidant properties.
SAR502250 is a potent, selective, ATP competitive, orally active and brain-penetrant inhibitor of GSK3, with an IC50 of 12 nM for human GSK-3β. SAR502250 displays antidepressant-like activity. SAR502250 can be used for the research of Alzheimer’s disease (AD)[1][2]. SAR502250 (0.01-1 μM; 36 h) attenuates the Aβ25-35-induced cell death in rat embryonic hippocampal neurons[2]. SAR502250 (1-100 mg kg; a single p.o,) attenuates tau hyperphosphorylation in the cortex and spinal cord of transgenic mice expressing P301L tau[2].SAR502250 (10-30 mg kg; p.o. once daily for 7 weeks) improves the cognitive deficit in transgenic APP(SW) Tau(VLW) mice after infusion of Aβ25-35[2].SAR502250 (10-30 mg kg; a single p.o.) significantly increases the percentage of lever-presses in the inter-response time (IRT) bin (49-96 s), with a significant augmentation of the percentage of reinforced responses[2].SAR502250 (30 mg kg; i.p. once daily for 28 d) ameliorates chronic stress-induced degradation of the physical state of the mice coat[2].SAR502250 (10-60 mg kg; a single p.o.) decreases hyperactivity produced by psychostimulantsin mice[2]. [1]. Fukunaga K, et, al. 2-(2-Phenylmorpholin-4-yl)pyrimidin-4(3H)-ones; a new class of potent, selective and orally active glycogen synthase kinase-3β inhibitors. Bioorg Med Chem Lett. 2013 Dec 15;23(24):6933-7.[2]. Griebel G, et, al. The selective GSK3 inhibitor, SAR502250, displays neuroprotective activity and attenuates behavioral impairments in models of neuropsychiatric symptoms of Alzheimer’s disease in rodents. Sci Rep. 2019 Dec 2;9(1):18045.
(E)-Ajoene is a disulfide that has been found inA. sativumand has diverse biological activities.1,2,3,4It is active against Gram-positive and Gram-negative bacteria (MICs = 10-250 and 150->500 μg/ml, respectively) and fungi (MICs = 15-50 μg/ml).1(E)-Ajoene inhibits proliferation of a variety of cancer cells, including MDA-MB-231 breast, HeLa cervical, and WHCO1 esophageal cancer cells (IC50s = 18.6, 61, and 39.2 μM, respectively).2It also inhibits human glutathione reductase andT. cruzitrypanothione reductase when used at a concentration of 200 μM.3(E)-Ajoene (25 mg/kg) is neuroprotective in a gerbil model of ischemia-reperfusion injury, reducing reactive astrocytosis and microgliosis in the hippocampal CA1 region.4 1.Yoshida, H., Iwata, N., Katsuzaki, H., et al.Antimicrobial activity of a compound isolated from an oil-macerated garlic extractBiosci. Biotechnol. Biochem.62(5)1014-1017(1998) 2.Kaschula, C.H., Hunter, R., Hassan, H.T., et al.Anti-proliferation activity of synthetic ajoene analogues on cancer cell-linesAnticancer Agents Med. Chem.11(3)260-266(2011) 3.Gallwitz, H., Bonse, S., Martinez-Cruz, A., et al.Ajoene is an inhibitor and subversive substrate of human glutathione reductase and Trypanosoma cruzi trypanothione reductase: Crystallographic, kinetic, and spectroscopic studiesJ. Med. Chem.42(3)364-372(1999) 4.Yoo, D.Y., Kim, W., Nam, S.M., et al.Neuroprotective effects of Z-ajoene, an organosulfur compound derived from oil-macerated garlic, in the gerbil hippocampal CA1 region after transient forebrain ischemiaFood Chem. Toxicol.721-7(2014)