Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
University of Science and Technology, Biomedical Sciences Program, Zewail City of Science and Technology, October Gardens, sixth of October, Giza 12578, Egypt.
J Med Chem. 2021 Jun 24;64(12):7926-7962. doi: 10.1021/acs.jmedchem.0c02265. Epub 2021 Jun 2.
Since their discovery as distinct receptor proteins, the specific physiopathological role of sigma receptors (σRs) has been deeply investigated. It has been reported that these proteins, classified into two subtypes indicated as σ and σ, might play a pivotal role in cancer growth, cell proliferation, and tumor aggressiveness. As a result, the development of selective σR ligands with potential antitumor properties attracted significant attention as an emerging theme in cancer research. This perspective deals with the recent advances of σR ligands as novel cytotoxic agents, covering articles published between 2010 and 2020. An up-to-date description of the medicinal chemistry of selective σR and σR ligands with antiproliferative and cytotoxic activities has been provided, including major pharmacophore models and comprehensive structure-activity relationships for each main class of σR ligands.
自被发现为独特的受体蛋白以来，sigma 受体（σRs）的特定生理病理学作用一直受到深入研究。据报道，这些蛋白可分为两个亚型，分别表示为 σ 和 σ，可能在癌症生长、细胞增殖和肿瘤侵袭性方面发挥关键作用。因此，开发具有潜在抗肿瘤特性的选择性 σR 配体作为癌症研究中的一个新兴主题引起了极大关注。本观点涉及作为新型细胞毒性剂的 σR 配体的最新进展，涵盖了 2010 年至 2020 年期间发表的文章。提供了具有抗增殖和细胞毒性活性的选择性 σR 和 σR 配体的药物化学的最新描述，包括主要药效团模型和每个主要 σR 配体类别的综合结构-活性关系。
