College of Pharmaceutical Sciences, Government Medical College, Thiruvananthapuram, Kerala, 695011, India.
Department of Biochemistry, St. Thomas College, Pala, Kottayam, Kerala, 686574, India.
Neurochem Res. 2024 Jun;49(6):1518-1528. doi: 10.1007/s11064-023-04031-6. Epub 2023 Oct 9.
Chalcones (trans-1,3-diphenyl-2-propen-1-ones) form simple chemical structures that act as precursors for the biogenesis of flavonoids. These are distributed in plants and have two aromatic or heteroaromatic rings connected by a three-carbon α, β-unsaturated carbonyl group. Considering the importance of chalcones as monoamine oxidase and acetylcholinesterase inhibitors, the study was designed as a comprehensive and systematic analysis to evaluate the pharmacological activities leading to the formation of drug molecules against Alzheimer's disease (AD). Based on our previous research, 11 indolyl chalcones (IC1-IC11) were synthesised and investigated for MAO-B inhibitory activity. The inhibitory potential was evaluated based on binding and reversibility studies using purified enzymes. The active and most promising molecule, (2E)-3-(4-bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one (IC9), also found predominant acetylcholinesterase inhibition and hence it was found dual acting in vitro. Based on this, the molecule IC9 was further subjected to cell line studies to further explore its role as a neuroprotective agent against neuronal degeneration, one of the main contributing parameters related to AD.
查耳酮（反式-1,3-二苯基-2-丙烯-1-酮）形成简单的化学结构，作为类黄酮生物合成的前体。这些存在于植物中，具有由三个碳原子的α、β-不饱和羰基连接的两个芳基或杂芳基环。鉴于查耳酮作为单胺氧化酶和乙酰胆碱酯酶抑制剂的重要性，本研究旨在进行全面系统的分析，以评估导致形成治疗阿尔茨海默病（AD）药物分子的药理活性。基于我们之前的研究，合成了 11 种吲哚基查耳酮（IC1-IC11），并研究了它们对 MAO-B 的抑制活性。根据使用纯化酶进行的结合和可逆性研究来评估抑制潜力。活性和最有前途的分子，（2E）-3-（4-溴苯基）-1-（1H-吲哚-3-基）丙-2-烯-1-酮（IC9），也发现具有明显的乙酰胆碱酯酶抑制作用，因此在体外具有双重作用。基于此，进一步对该分子 IC9 进行了细胞系研究，以进一步探索其作为神经保护剂对抗神经元变性的作用，神经元变性是与 AD 相关的主要参数之一。
