Modh Dharti H, Kulkarni Vithal M
Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be) University, Erandwane, Pune, 411038, Maharashtra, India.
Mini Rev Med Chem. 2024;24(1):60-91. doi: 10.2174/1389557523666230509123036.
Despite the tremendous progress that has occurred in recent years in cell biology and oncology, in chemical, physical and computer sciences, the disease cancer has continued as the major cause of death globally. Research organizations, academic institutions and pharmaceutical companies invest huge amounts of money in the discovery and development of new anticancer drugs. Though much effort is continuing and whatever available approaches are being attempted, the success of bringing one effective drug into the market has been uncertain. To overcome problems associated with drug discovery, several approaches are being attempted. One such approach has been the use of known, approved and marketed drugs to screen these for new indications, which have gained considerable interest. This approach is known in different terms as "drug repositioning or drug repurposing." Drug repositioning refers to the structure modification of the active molecule by synthesis, in vitro/ in vivo screening and in silico computational applications where macromolecular structure-based drug design (SBDD) is employed. In this perspective, we aimed to focus on the application of repositioning or repurposing of essential drug moieties present in drugs that are already used for the treatment of some diseases such as diabetes, human immunodeficiency virus (HIV) infection and inflammation as anticancer agents. This review thus covers the available literature where molecular modeling of drugs/enzyme inhibitors through SBDD is reported for antidiabetics, anti-HIV and inflammatory diseases, which are structurally modified and screened for anticancer activity using respective cell lines.
尽管近年来细胞生物学、肿瘤学以及化学、物理和计算机科学取得了巨大进展，但癌症仍是全球主要的死亡原因。研究机构、学术团体和制药公司投入大量资金用于发现和开发新的抗癌药物。尽管仍在持续付出诸多努力并尝试各种可行的方法，但将一种有效药物推向市场的成功率仍不确定。为克服与药物研发相关的问题，人们尝试了多种方法。其中一种方法是利用已知的、已获批上市的药物来筛选新的适应症，这种方法已引起了广泛关注。这种方法有不同的称谓，如“药物重新定位”或“药物再利用”。药物重新定位是指通过合成、体外/体内筛选以及采用基于大分子结构的药物设计（SBDD）的计算机模拟计算应用对活性分子进行结构修饰。从这个角度出发，我们旨在关注那些已用于治疗某些疾病（如糖尿病、人类免疫缺陷病毒（HIV）感染和炎症）的药物中必需药物部分作为抗癌剂的重新定位或再利用的应用。因此，本综述涵盖了现有文献，这些文献报道了通过SBDD对药物/酶抑制剂进行分子建模，用于抗糖尿病、抗HIV和炎症性疾病，对其进行结构修饰并使用相应细胞系筛选抗癌活性。
