Compounds for treatment of alzheimer’s disease

The invention relates to certain chromanol, quinone or hydroquinone compounds and ‘ derivatives thereof for treatment of Alzheimer’s disease and/or for improving memory , function. Specifically, the present invention relates to chromanol compounds chosen from (6— \ 5 hydroxy-2,5,7,8—tetramethylchroman—Zyl)(piperazin-l -yl)methanone, ((S)-6-hydroxy-2,5,7,8~ tetramethyl—N—((R)-piperidin—3—yl)chroman—2—carboxamide hydrochloride and S-(6—hydroxy— 2,5 ,7, 8~tetramethylchroman—2-yl)(4-(2—hydroxyethyl)piperazin- 1 -y1)methanone, and pharmaceutically acceptable salts thereof

The novel compound Sul-121 inhibits airway inflammation and hyperresponsiveness in experimental models of chronic obstructive pulmonary disease

COPD is characterized by persistent airflow limitation, neutrophilia and oxidative stress from endogenous and exogenous insults. Current COPD therapy involving anticholinergics, beta(2)-adrenoceptor agonists and/or corticosteroids, do not specifically target oxidative stress, nor do they reduce chronic pulmonary inflammation and disease progression in all patients. Here, we explore the effects of Sul-121, a novel compound with anti-oxidative capacity, on hyperresponsiveness (AHR) and inflammation in experimental models of COPD. Using a guinea pig model of lipopolysaccharide (LPS)-induced neutrophilia, we demonstrated that Sul-121 inhalation dose-dependently prevented LPS-induced airway neutrophilia (up to similar to 60%) and AHR (up to similar to 90%). Non-cartilaginous airways neutrophilia was inversely correlated with blood H2S, and LPS-induced attenuation of blood H2S (similar to 60%) was prevented by Sul-121. Concomitantly, Sul-121 prevented LPS-induced production of the oxidative stress marker, malondialdehyde by similar to 80%. In immortalized human airway smooth muscle (ASM) cells, Sul-121 dose-dependently prevented cigarette smoke extract-induced IL-8 release parallel with inhibition of nuclear translocation of the NF-kappa B subunit, p65 (each similar to 90%). Sul-121 also diminished cellular reactive oxygen species production in ASM cells, and inhibited nuclear translocation of the anti-oxidative response regulator, Nrf2. Our data show that Sul-121 effectively inhibits airway inflammation and AHR in experimental COPD models, prospectively through inhibition of oxidative stress

Compounds for treatment of alzheimer’s disease

The invention relates to certain chromanol, quinone or hydroquinone compounds and ‘ derivatives thereof for treatment of Alzheimer’s disease and/or for improving memory , function. Specifically, the present invention relates to chromanol compounds chosen from (6— \ 5 hydroxy-2,5,7,8—tetramethylchroman—Zyl)(piperazin-l -yl)methanone, ((S)-6-hydroxy-2,5,7,8~ tetramethyl—N—((R)-piperidin—3—yl)chroman—2—carboxamide hydrochloride and S-(6—hydroxy— 2,5 ,7, 8~tetramethylchroman—2-yl)(4-(2—hydroxyethyl)piperazin- 1 -y1)methanone, and pharmaceutically acceptable salts thereof

The 6-chromanol derivate SUL-109 enables prolonged hypothermic storage of adipose tissue-derived stem cells

Encouraging advances in cell therapy research with adipose derived stem cells (ASC) require an effective short-term preservation method that provides time for quality control and transport of cells from their manufacturing facility to their clinical destination. Hypothermic storage of cells in their specific growth media offers an alternative and simple preservation method to liquid nitrogen cryopreservation or commercial preservation fluids for short-term storage and transport. However, accumulation of cell damage during hypothermia may result in cell injury and death upon rewarming through the production of excess reactive oxygen species (ROS). Here, the ability of the cell culture medium additive SUL-109, a modified 6-chromanol, to protect ASC from hypothermia and rewarming damage is examined. SUL-109 conveys protective effects against cold-induced damage in ASC as is observed by preservation of cell viability, adhesion properties and growth potential. SUL-109 does not reduce the multilineage differentiation capacity of ASC. SUL-109 conveys its protection against hypothermic damage by the preservation of the mitochondrial membrane potential through the activation of mitochondrial membrane complexes I and IV, and increases maximal oxygen consumption in FCCP uncoupled mitochondria. Consequently, SUL-109 alleviates mitochondrial ROS production and preserves ATP production. In summary, here we describe the generation of a single molecule cell preservation agent that protects ASC from hypothermic damage associated with short-term cell preservation that does not affect the differentiation capacity of ASC. (C) 2016 Elsevier Ltd. All rights reserved