Xu Shi, Shieh Meg, Paul Bindu D, Xian Ming
Department of Chemistry, Brown University, Providence, Rhode Island, USA.
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Br J Pharmacol. 2023 Aug 8. doi: 10.1111/bph.16211.
Hydrogen sulfide (H S) is an important gaseous signalling molecule known to be critically involved in regulating cellular redox homeostasis. As the beneficial and therapeutic effects of H S in pathophysiology, such as in cardiovascular and neurodegenerative diseases, have emerged, so too has the drive for the development of H S-releasing compounds (aka donors) and their therapeutic applications. Most reported donor compounds singularly release H S through biocompatible triggers. An emerging area in the field is the development of compounds that can co-deliver H S with other drugs or biologically relevant species, such as reactive oxygen and nitrogen species (ROS and RNS, respectively). These H S-based dual donors and hybrid drugs are expected to offset negative side effects from individual treatments or achieve synergistic effects rendering them more clinically effective. Additionally, considering that molecules exist and interact physiologically, dual donors may more accurately mimic biological systems as compared to single donors and allow for the elucidation of fundamental chemistry and biology. This review focuses on the recent advances in the development of H S-based dual donors and hybrid drugs along with their design principles and synergistic effects.
硫化氢（H₂S）是一种重要的气体信号分子，已知其在调节细胞氧化还原稳态中起关键作用。随着硫化氢在病理生理学（如心血管疾病和神经退行性疾病）中的有益和治疗作用逐渐显现，开发硫化氢释放化合物（即供体）及其治疗应用的需求也随之而来。大多数已报道的供体化合物通过生物相容性触发机制单独释放硫化氢。该领域一个新兴的方向是开发能够将硫化氢与其他药物或生物相关物质（如活性氧和活性氮物种，分别为ROS和RNS）共同递送的化合物。这些基于硫化氢的双供体和杂合药物有望抵消单一治疗的负面副作用或实现协同效应，使其在临床上更有效。此外，考虑到分子在生理上的存在和相互作用，与单供体相比，双供体可能更准确地模拟生物系统，并有助于阐明基础化学和生物学。本综述重点介绍了基于硫化氢的双供体和杂合药物开发的最新进展及其设计原则和协同效应。
