Shen Yan, Qiang Shengsheng, Ma Shutao
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, China.
Mini Rev Med Chem. 2015;15(10):837-57. doi: 10.2174/1389557515666150511152433.
Cancer is a serious disease characterized by the uncontrolled growth division of cells, and nowadays it remains a significant challenge for the medical field. Malaria is an infectious disease in the similar situation to cancer. Almost 40% people in the world live in areas with malaria risk and each year there are about 2 to 3 million people dying from malaria. Farnesyltransferase (FTase) that belongs to isoprenyltransferase family can catalyze the initial step of Ras-processing and is identified as a promising target for the treatment of cancer and malaria. During the past decade years, a large number of FTase inhibitors with anticancer or antimalarial activity have been reported and some of them are undergoing clinical development. This review mainly introduces the FTase inhibitors as anticancer and antimalarial agents, with focus on their enzyme inhibitory activity, stability and enzyme selectivity, etc. In particular, the promising new FTase inhibitors among them will be discussed in detail and the inspirations for their design will be highlighted.
癌症是一种以细胞不受控制的生长分裂为特征的严重疾病，如今它仍然是医学领域的一项重大挑战。疟疾是一种与癌症情况类似的传染病。世界上近40%的人生活在有疟疾风险的地区，每年约有200万至300万人死于疟疾。属于异戊二烯基转移酶家族的法尼基转移酶（FTase）可以催化Ras加工的第一步，被确定为治疗癌症和疟疾的一个有前景的靶点。在过去十年中，已经报道了大量具有抗癌或抗疟活性的FTase抑制剂，其中一些正在进行临床开发。本综述主要介绍作为抗癌和抗疟药物的FTase抑制剂，重点关注它们的酶抑制活性、稳定性和酶选择性等。特别是，将详细讨论其中有前景的新型FTase抑制剂，并突出其设计灵感。
