Zhu Haizhou, Dronamraju Venkateshwara, Xie Wei, More Swati S
Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
Med Chem Res. 2021 Feb;30(2):305-352. doi: 10.1007/s00044-020-02687-1. Epub 2021 Jan 15.
Sulfur is widely existent in natural products and synthetic organic compounds as organosulfur, which are often associated with a multitude of biological activities. OBenzothiazole, in which benzene ring is fused to the 4,5-positions of the thiazolerganosulfur compounds continue to garner increasing amounts of attention in the field of medicinal chemistry, especially in the development of therapeutic agents for Alzheimer's disease (AD). AD is a fatal neurodegenerative disease and the primary cause of age-related dementia posing severe societal and economic burdens. Unfortunately, there is no cure for AD. A lot of research has been conducted on sulfur-containing compounds in the context of AD due to their innate antioxidant potential and some are currently being evaluated in clinical trials. In this review, we have described emerging trends in the field, particularly the concept of multi-targeting and formulation of disease-modifying strategies. SAR, pharmacological targets, in vitro/vivo ADMET, efficacy in AD animal models, and applications in clinical trials of such sulfur compounds have also been discussed. This article provides a comprehensive review of organosulfur-based AD therapeutic agents and provides insights into their future development.
硫以有机硫的形式广泛存在于天然产物和合成有机化合物中,这些有机硫通常具有多种生物活性。苯并噻唑中苯环与噻唑的4,5位稠合,有机硫化合物在药物化学领域不断受到越来越多的关注,尤其是在阿尔茨海默病(AD)治疗药物的开发方面。AD是一种致命的神经退行性疾病,也是与年龄相关痴呆的主要原因,给社会和经济带来了沉重负担。不幸的是,目前尚无治愈AD的方法。由于含硫化合物具有固有的抗氧化潜力,因此在AD背景下对其进行了大量研究,目前一些化合物正在进行临床试验评估。在这篇综述中,我们描述了该领域的新趋势,特别是多靶点概念和疾病修饰策略的制定。还讨论了这类硫化合物的构效关系、药理靶点、体外/体内药物代谢动力学及毒性、在AD动物模型中的疗效以及在临床试验中的应用。本文对基于有机硫的AD治疗药物进行了全面综述,并对其未来发展提供了见解。