Lesniewska-Kowiel Monika A, Muszalska Izabela
Poznan University of Medical Sciences, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Grunwaldzka Str. 6, 60-780, Poznań, Poland.
Poznan University of Medical Sciences, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Grunwaldzka Str. 6, 60-780, Poznań, Poland.
Eur J Med Chem. 2017 Mar 31;129:53-71. doi: 10.1016/j.ejmech.2017.02.011. Epub 2017 Feb 9.
Prodrugs are a wide group of substances of low or no pharmacological activity. The search for prodrugs is aimed at obtaining drugs characterized by better pharmacokinetic properties, pharmaceutical availability and selective activity of the active substance. Prodrug strategies involve chemical modifications and syntheses of new structures as well as the establishment of systems that deliver active substances for therapeutic aims that is prodrug-based treatments. The paper describes decisive factors in prodrug designing, such as enzymes participating in their activation, concepts of chemical modifications in the group of antiviral drugs and new anticancer treatments based on prodrugs (ADEPT, GDEPT, LEAPT). Prodrugs are seen as a possibility to design medicines which are selective for their therapeutic aim, for example a tumorous cell or a microorganism. Such an approach is possible thanks to the knowledge on: pathogenesis of diseases at molecular level, metabolism of healthy and affected cells as well as metabolism of microorganisms (bacteria, fungi, protozoa, etc.). Many drugs which have been used for years are still studied in relation to their metabolism and their molecular mechanism of operation, providing new knowledge on active substances. Many of them meet the criteria of being a prodrug. The paper indicates methods of discovering new structures or modifications of known structures and their synthesis as well as new therapeutic strategies using prodrugs, which are expected to be successful and to broaden the knowledge on what is happening to the drug in the body, in addition to providing a molecular explanation of xenobiotics activity.
前药是一大类药理活性低或无药理活性的物质。寻找前药的目的是获得具有更好药代动力学性质、药物可及性和活性物质选择性活性的药物。前药策略包括化学修饰和新结构的合成，以及建立用于治疗目的的活性物质递送系统，即基于前药的治疗方法。本文描述了前药设计中的决定性因素，例如参与其活化的酶、抗病毒药物组中的化学修饰概念以及基于前药的新抗癌治疗方法（ADEPT、GDEPT、LEAPT）。前药被视为设计针对其治疗目标具有选择性的药物的一种可能性，例如肿瘤细胞或微生物。由于在分子水平上对疾病发病机制、健康细胞和受影响细胞的代谢以及微生物（细菌、真菌、原生动物等）代谢的了解，这种方法是可行的。许多已使用多年的药物仍在对其代谢及其分子作用机制进行研究，从而提供有关活性物质的新知识。其中许多符合前药的标准。本文指出了发现新结构或已知结构修饰及其合成的方法，以及使用前药的新治疗策略，这些策略有望取得成功并拓宽对药物在体内情况的认识，此外还能提供对外源化合物活性的分子解释。
