Department of Chemistry, Bar Ilan University, Ramat Gan 52900, Israel.
Curr Med Chem. 2023;30(38):4283-4339. doi: 10.2174/0929867330666221209102650.
This review encapsulates an extensive variety of substances identified as mutual prodrugs or codrugs, wherein two, or sometimes three, biologically active moieties are linked using an assortment of metabolically unstable bridging entities. Following the administration of the mutual prodrugs, these undergo a bridge cleavage releasing the active molecules, which then elicit their respective biological effects. In some cases, the released drugs act synergistically, other times the biological activity of only one of the drugs is elicited, and in such cases, the accompanying drug serves only as a carrier, which may have an affinity to the desired receptor. The most promising results are commonly observed when the two released drugs are efficacious at similar concentrations and particularly when the two drugs are effective against similar diseases. For instance, the best results are observed, when two analgesics, two anticancer agents, two drugs for the treatment of cardiac conditions, etc., are the substances comprising the codrug. Mutual prodrugs/ codrugs described herein have been reported, primarily since the year 2000, as potential drugs for use against a plethora of diseases including pain, inflammation, cancer, bacterial infections, sickle cell anemia, Alzheimer's disease, and others.
这篇综述涵盖了大量被确定为相互前药或共前药的物质，其中两种，有时是三种，生物活性部分通过各种代谢不稳定的桥接实体连接在一起。在给予相互前药后，这些前药会发生桥裂解，释放出活性分子，然后发挥各自的生物学效应。在某些情况下，释放的药物会协同作用，而在其他情况下，只有一种药物会发挥其生物学活性，在这种情况下，伴随的药物仅作为载体，可能对所需的受体具有亲和力。当两种释放的药物以相似的浓度有效且特别是当两种药物对相似的疾病有效时，通常会观察到最有前途的结果。例如，当两种镇痛药、两种抗癌药物、两种治疗心脏病的药物等作为共药物的物质时，会观察到最佳的结果。本文所述的相互前药/共前药主要自 2000 年以来被报道为用于治疗多种疾病的潜在药物，包括疼痛、炎症、癌症、细菌感染、镰状细胞贫血、阿尔茨海默病等。
