Drug Discovery Program, Midwest Veterans' Biomedical Research Foundation, KCVA Medical Center, Kansas City, MO 64128, USA.
Drug Discovery Program, Midwest Veterans' Biomedical Research Foundation, KCVA Medical Center, Kansas City, MO 64128, USA.
Bioorg Chem. 2021 Mar;108:104681. doi: 10.1016/j.bioorg.2021.104681. Epub 2021 Jan 29.
Chalcone [(E)-1,3-diphenyl-2-propene-1-one], a small molecule with α, β unsaturated carbonyl group is a precursor or component of many natural flavonoids and isoflavonoids. It is one of the privileged structures in medicinal chemistry. It possesses a wide range of biological activities encouraging many medicinal chemists to study this scaffold for its usefulness to oncology, infectious diseases, virology and neurodegenerative diseases including Alzheimer's disease (AD). Small molecular size, convenient and cost-effective synthesis, and flexibility for modifications to modulate lipophilicity suitable for blood brain barrier (BBB) permeability make chalcones a preferred candidate for their therapeutic and diagnostic potential in AD. This review summarizes and highlights the importance of chalcone and its analogs as single target small therapeutic agents, multi-target directed ligands (MTDLs) as well as molecular imaging agents for AD. The information summarized here will guide many medicinal chemist and researchers involved in drug discovery to consider chalcone as a potential scaffold for the development of anti-AD agents including theranostics.
查耳酮[(E)-1,3-二苯基-2-丙烯-1-酮],一种具有α,β不饱和羰基的小分子,是许多天然类黄酮和异黄酮的前体或组成部分。它是药物化学中的一种优势结构。它具有广泛的生物活性,这促使许多药物化学家研究这种支架,以将其用于肿瘤学、传染病、病毒学和神经退行性疾病,包括阿尔茨海默病(AD)。小分子尺寸、方便且具有成本效益的合成以及对调节亲脂性以适合血脑屏障(BBB)通透性的修饰的灵活性,使查耳酮成为治疗和诊断 AD 方面具有治疗潜力的首选候选物。本综述总结并强调了查耳酮及其类似物作为单一靶标小分子治疗剂、多靶标导向配体(MTDLs)以及用于 AD 的分子成像剂的重要性。这里总结的信息将指导许多参与药物发现的药物化学家考虑将查耳酮作为开发抗 AD 药物的潜在支架,包括治疗学。