Kittakoop Prasat, Mahidol Chulabhorn, Ruchirawat Somsak
Chulabhorn Research Institute, Kamphaeng Phet 6 Road, Laksi, Bangkok 10210, Thailand.
Curr Top Med Chem. 2014;14(2):239-52. doi: 10.2174/1568026613666131216105049.
Alkaloid molecules can act, depending on a type of amine functionality present in alkalods, as either hydrogenacceptor or hydrogen-donor for hydrogen bonding that is critically important for the interaction (binding) between targets (enzymes, proteins and receptors) and drugs (ligands). Because of this unique property, alkaloid scaffolds are therefore present in several drugs and lead compounds. This review highlights alkaloid scaffolds in drugs, particularly those recently approved in 2012; it also covers the scaffolds in leads and drug candidates which are in clinical trials and preclinical pipeline. The review focuses on three therapeutic areas including treatments of cancer, tuberculosis, and tobacco cessation. Alkaloid scaffolds in drugs and leads are inspired by those of naturally occurring alkaloids, and these scaffolds include pyridine, piperidine, quinoline, quinolinone, quinazoline, isoquinoline, indole, indolinone, isoindole, isoxazole, imidazole, indazole, thiazole, pyrazole, oxazolidinone, oxadiazole, and benzazepine. In addition to medicinal chemistry aspects, natural products possessing an individual alkaloid scaffold, as well as the mechanism of action of drugs and leads, are also discussed in this review.
生物碱分子可根据生物碱中存在的胺官能团类型，作为氢键的氢受体或氢供体，而氢键对于靶点（酶、蛋白质和受体）与药物（配体）之间的相互作用（结合）至关重要。由于这一独特性质，生物碱骨架因此存在于多种药物和先导化合物中。本综述重点介绍了药物中的生物碱骨架，特别是2012年最近获批的那些；还涵盖了处于临床试验和临床前研发阶段的先导化合物和候选药物中的骨架。该综述聚焦于三个治疗领域，包括癌症治疗、结核病治疗和戒烟。药物和先导化合物中的生物碱骨架受到天然生物碱骨架的启发，这些骨架包括吡啶、哌啶、喹啉、喹啉酮、喹唑啉、异喹啉、吲哚、吲哚酮、异吲哚、异恶唑、咪唑、吲唑、噻唑、吡唑、恶唑烷酮、恶二唑和苯并氮杂卓。除了药物化学方面，本综述还讨论了具有单个生物碱骨架的天然产物，以及药物和先导化合物的作用机制。
