González-Andrés Paula, Fernández-Peña Laura, Díez-Poza Carlos, Villalobos Carlos, Nuñez Lucía, Barbero Asunción
Department of Organic Chemistry, Campus Miguel Delibes, University of Valladolid, 47011 Valladolid, Spain.
Institute of Biology and Molecular Genetics (IBGM), University of Valladolid and Spanish National Research Council (CSIC), 47003 Valladolid, Spain.
Mar Drugs. 2021 Jan 31;19(2):78. doi: 10.3390/md19020078.
Intracellular Ca plays a pivotal role in the control of a large series of cell functions in all types of cells, from neurotransmitter release and muscle contraction to gene expression, cell proliferation and cell death. Ca is transported through specific channels and transporters in the plasma membrane and subcellular organelles such as the endoplasmic reticulum and mitochondria. Therefore, dysregulation of intracellular Ca homeostasis may lead to cell dysfunction and disease. Accordingly, chemical compounds from natural origin and/or synthesis targeting directly or indirectly these channels and proteins may be of interest for the treatment of cell dysfunction and disease. In this review, we show an overview of a group of marine drugs that, from the structural point of view, contain one or various heterocyclic units in their core structure, and from the biological side, they have a direct influence on the transport of calcium in the cell. The marine compounds covered in this review are divided into three groups, which correspond with their direct biological activity, such as compounds with a direct influence in the calcium channel, compounds with a direct effect on the cytoskeleton and drugs with an effect on cancer cell proliferation. For each target, we describe its bioactive properties and synthetic approaches. The wide variety of chemical structures compiled in this review and their significant medical properties may attract the attention of many different researchers.
细胞内钙在控制各类细胞的一系列细胞功能中起着关键作用,从神经递质释放、肌肉收缩到基因表达、细胞增殖和细胞死亡。钙通过质膜以及内质网和线粒体等亚细胞器中的特定通道和转运蛋白进行运输。因此,细胞内钙稳态的失调可能导致细胞功能障碍和疾病。相应地,直接或间接靶向这些通道和蛋白质的天然来源和/或合成的化合物可能对治疗细胞功能障碍和疾病具有重要意义。在本综述中,我们概述了一类海洋药物,从结构角度来看,它们的核心结构中含有一个或多个杂环单元,从生物学角度来看,它们对细胞内钙的运输有直接影响。本综述涵盖的海洋化合物分为三组,这与它们的直接生物学活性相对应,例如对钙通道有直接影响的化合物、对细胞骨架有直接作用的化合物以及对癌细胞增殖有影响的药物。对于每个靶点,我们描述了其生物活性特性和合成方法。本综述中汇编的各种化学结构及其显著的医学特性可能会吸引许多不同研究人员的关注。