Department of Clinical Biochemistry, University of Kashmir, Srinagar 190006, India.
Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia.
Int J Mol Sci. 2022 Mar 18;23(6):3305. doi: 10.3390/ijms23063305.
Tricyclodecan-9-yl xanthogenate (D609) is a synthetic tricyclic compound possessing a xanthate group. This xanthogenate compound is known for its diverse pharmacological properties. Over the last three decades, many studies have reported the biological activities of D609, including antioxidant, antiapoptotic, anticholinergic, anti-tumor, anti-inflammatory, anti-viral, anti-proliferative, and neuroprotective activities. Its mechanism of action is extensively attributed to its ability to cause the competitive inhibition of phosphatidylcholine (PC)-specific phospholipase C (PC-PLC) and sphingomyelin synthase (SMS). The inhibition of PCPLC or SMS affects secondary messengers with a lipidic nature, i.e., 1,2-diacylglycerol (DAG) and ceramide. Various in vitro/in vivo studies suggest that PCPLC and SMS inhibition regulate the cell cycle, block cellular proliferation, and induce differentiation. D609 acts as a pro-inflammatory cytokine antagonist and diminishes Aβ-stimulated toxicity. PCPLC enzymatic activity essentially requires Zn, and D609 might act as a potential chelator of Zn, thereby blocking PCPLC enzymatic activity. D609 also demonstrates promising results in reducing atherosclerotic plaque formation, post-stroke cerebral infarction, and cancer progression. The present compilation provides a comprehensive mechanistic insight into D609, including its chemistry, mechanism of action, and regulation of various pharmacological activities.
三环癸烷-9-基黄原酸酯(D609)是一种具有黄原酸酯基团的合成三环化合物。这种黄原酸酯化合物因其多种药理学特性而闻名。在过去的三十年中,许多研究报告了 D609 的生物活性,包括抗氧化、抗凋亡、抗胆碱能、抗肿瘤、抗炎、抗病毒、抗增殖和神经保护活性。其作用机制广泛归因于其能够引起磷脂酰胆碱(PC)特异性磷脂酶 C(PC-PLC)和鞘磷脂合酶(SMS)的竞争性抑制。PCPLC 或 SMS 的抑制作用会影响具有脂质性质的二级信使,即 1,2-二酰基甘油(DAG)和神经酰胺。各种体外/体内研究表明,PCPLC 和 SMS 抑制调节细胞周期,阻止细胞增殖并诱导分化。D609 作为促炎细胞因子拮抗剂,可减轻 Aβ刺激的毒性。PCPLC 酶活性本质上需要 Zn,而 D609 可能作为 Zn 的潜在螯合剂,从而阻断 PCPLC 酶活性。D609 在减少动脉粥样硬化斑块形成、中风后脑梗死和癌症进展方面也显示出有希望的结果。本综述提供了对 D609 的全面机制见解,包括其化学、作用机制以及对各种药理学活性的调节。