Ipe Reshma Susan, Kumar Sunil, Benny Feba, Jayan Jayalakshmi, Manoharan Amritha, Sudevan Sachitra Thazhathuveedu, George Ginson, Gahtori Prashant, Kim Hoon, Mathew Bijo
Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi 682041, India.
School of Pharmacy, Graphic Era Hill University, Dehradun 248007, India.
Pharmaceuticals (Basel). 2023 Sep 15;16(9):1310. doi: 10.3390/ph16091310.
Monoamine oxidases (MAOs) are a family of flavin adenine dinucleotide-dependent enzymes that catalyze the oxidative deamination of a wide range of endogenous and exogenous amines. Multiple neurological conditions, including Parkinson's disease (PD) and Alzheimer's disease (AD), are closely correlated with altered biogenic amine concentrations in the brain caused by MAO. Toxic byproducts of this oxidative breakdown, including hydrogen peroxide, reactive oxygen species, and ammonia, can cause oxidative damage and mitochondrial dysfunction in brain cells. Certain MAO-B blockers have been recognized as effective treatment options for managing neurological conditions, including AD and PD. There is still a pressing need to find potent therapeutic molecules to fight these disorders. However, the focus of neurodegeneration studies has recently increased, and certain compounds are now in clinical trials. Chromones are promising structures for developing therapeutic compounds, especially in neuronal degeneration. This review focuses on the MAO-B inhibitory potential of several synthesized chromones and their structural activity relationships. Concerning the discovery of a novel class of effective chromone-based selective MAO-B-inhibiting agents, this review offers readers a better understanding of the most recent additions to the literature.
单胺氧化酶(MAOs)是一类黄素腺嘌呤二核苷酸依赖性酶,可催化多种内源性和外源性胺类的氧化脱氨反应。多种神经系统疾病,包括帕金森病(PD)和阿尔茨海默病(AD),都与MAO引起的大脑中生物胺浓度改变密切相关。这种氧化分解的有毒副产物,包括过氧化氢、活性氧和氨,可导致脑细胞的氧化损伤和线粒体功能障碍。某些MAO-B抑制剂已被公认为治疗包括AD和PD在内的神经系统疾病的有效选择。目前仍迫切需要找到有效的治疗分子来对抗这些疾病。然而,最近神经退行性变研究的重点有所增加,某些化合物现已进入临床试验阶段。色酮是开发治疗化合物的有前景的结构,尤其是在神经元变性方面。本综述重点关注几种合成色酮的MAO-B抑制潜力及其构效关系。关于发现一类新型有效的基于色酮的选择性MAO-B抑制剂,本综述使读者能更好地了解该领域文献中的最新进展。