Casertano Marcello, Vito Alessio, Aiello Anna, Imperatore Concetta, Menna Marialuisa
Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, 80131 Napoli, Italy.
Pharmaceutics. 2023 Sep 14;15(9):2321. doi: 10.3390/pharmaceutics15092321.
Type 2 diabetes mellitus (T2DM) is an ongoing, risky, and costly health problem that therefore always requires new treatment options. Moreover, although several drugs are available, only 36% of patients achieve glycaemic control, and patient adherence is a major obstacle. With monotherapy, T2DM and its comorbidities/complications often cannot be managed, and the concurrent administration of several hypoglycaemic drugs is required, which increases the risk of side effects. In fact, despite the efficacy of the drugs currently on the market, they generally come with serious side effects. Therefore, scientific research must always be active in the discovery of new therapeutic agents.
The present review highlights some of the recent discoveries regarding marine natural products that can modulate the various targets that have been identified as crucial in the establishment of T2DM disease and its complications, with a focus on the compounds isolated from marine invertebrates. The activities of these metabolites are illustrated and discussed.
The paper aims to capture the relevant evidence of the great chemical diversity of marine natural products as a key tool that can advance understanding in the T2DM research field, as well as in antidiabetic drug discovery. The variety of chemical scaffolds highlighted by the natural hits provides not only a source of chemical probes for the study of specific targets involved in the onset of T2DM, but is also a helpful tool for the development of drugs that are capable of acting via novel mechanisms. Thus, it lays the foundation for the design of multiple ligands that can overcome the drawbacks of polypharmacology.
2型糖尿病(T2DM)是一个持续存在、具有风险且成本高昂的健康问题,因此始终需要新的治疗选择。此外,尽管有几种药物可供使用,但只有36%的患者实现了血糖控制,患者依从性是一个主要障碍。采用单一疗法时,T2DM及其合并症/并发症往往无法得到控制,需要同时使用几种降糖药物,这增加了副作用的风险。事实上,尽管目前市场上的药物有效,但它们通常伴有严重的副作用。因此,科学研究必须始终积极致力于发现新的治疗药物。
本综述重点介绍了一些关于海洋天然产物的最新发现,这些产物可以调节在T2DM疾病及其并发症的发生过程中被确定为关键的各种靶点,重点是从海洋无脊椎动物中分离出的化合物。对这些代谢物的活性进行了说明和讨论。
本文旨在获取相关证据,证明海洋天然产物具有巨大的化学多样性,是推动T2DM研究领域以及抗糖尿病药物发现领域认识的关键工具。天然产物所突出的各种化学骨架不仅为研究T2DM发病过程中涉及的特定靶点提供了化学探针来源,也是开发能够通过新机制发挥作用的药物的有用工具。因此,它为设计能够克服多药理学缺点的多种配体奠定了基础。