Abstract

Cholinesterase (ChE) inhibitors are currently the main drugs used to treat the cognitive symptoms of Alzheimer’s disease (AD). Dual cholinesterase inhibitors, that is, compounds capable of inhibiting both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), are considered a new potential approach for the long-term treatment of patients with AD. We evaluated the ethyl acetate extract of Phomopsis sp., grown in liquid medium malt extract and potato dextrose (PDB), an endophyte isolated from the Brazilian medicinal plant Hancornia speciosa. The anticholinesterase (AChE) and butyrylcholinesterase (BuChE) activities were evaluated. The extracts exhibited dual action against AChE and BuChE. The compounds isolated from these extracts, nectriapyrone (1) and tryptophol (2), showed inhibitory action on BuChE (IC50 = 29.05 and 34.15 μM respectively), being selective towards BuChE. The discovery of selective BuChE inhibitors is extremely important for the development of drugs that can be used in the treatment of patients diagnosed with AD.

摘要

胆碱酯酶 (ChE) 抑制剂是目前用于治疗阿尔茨海默病 (AD) 认知症状的主要药物。双胆碱酯酶抑制剂，即能够同时抑制乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BuChE) 的化合物，被认为是长期治疗 AD 患者的一种新的潜在方法。我们评估了在液体培养基麦芽提取物和马铃薯葡萄糖 (PDB) 中生长的Phomopsis sp.的乙酸乙酯提取物，这是一种从巴西药用植物Hancornia speciosa中分离出来的内生菌. 评估了抗胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BuChE) 的活性。提取物表现出对 AChE 和 BuChE 的双重作用。从这些提取物中分离出的化合物 Nectriapyrone (1) 和色氨酸 (2) 对 BuChE 具有抑制作用（IC50 分别为 29.05 和 34.15 μM），对 BuChE 具有选择性。选择性 BuChE 抑制剂的发现对于开发可用于治疗诊断为 AD 患者的药物极为重要。