Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho, 45, 4200-135 Porto, Portugal.
Molecules. 2018 Sep 11;23(9):2318. doi: 10.3390/molecules23092318.
Although drugs currently used for the various types of diseases (e.g., antiparasitic, antiviral, antibacterial, etc.) are effective, they present several undesirable pharmacological and pharmaceutical properties. Most of the drugs have low bioavailability, lack of sensitivity, and do not target only the damaged cells, thus also affecting normal cells. Moreover, there is the risk of developing resistance against drugs upon chronic treatment. Consequently, their potential clinical applications might be limited and therefore, it is mandatory to find strategies that improve those properties of therapeutic agents. The development of prodrugs using amino acids as moieties has resulted in improvements in several properties, namely increased bioavailability, decreased toxicity of the parent drug, accurate delivery to target tissues or organs, and prevention of fast metabolism. Herein, we provide an overview of models currently in use of prodrug design with amino acids. Furthermore, we review the challenges related to the permeability of poorly absorbed drugs and transport and deliver on target organs.
虽然目前用于各种类型疾病（例如，抗寄生虫、抗病毒、抗菌等）的药物是有效的，但它们具有几种不理想的药理学和药物学特性。大多数药物的生物利用度低、缺乏敏感性，并且不仅针对受损细胞，还会影响正常细胞。此外，长期治疗还存在对药物产生耐药性的风险。因此，它们的潜在临床应用可能会受到限制，因此，有必要寻找能够改善治疗剂这些特性的策略。使用氨基酸作为部分的前药的开发导致了几个特性的改善，即增加生物利用度、降低母体药物的毒性、将药物准确递送到靶组织或器官，以及防止快速代谢。本文综述了目前使用氨基酸进行前药设计的模型。此外，我们还综述了与吸收不良药物的通透性以及向靶器官转运和输送相关的挑战。
