Department of Chemistry, Indian Institute of Technology (BHU), 221005, Varanasi, India.
ChemMedChem. 2023 Oct 4;18(19):e202300326. doi: 10.1002/cmdc.202300326. Epub 2023 Aug 4.
In antimalarial drug development research, overcoming drug resistance has been a major challenge for researchers. Nowadays, several drugs like chloroquine, mefloquine, sulfadoxine, and artemisinin are used to treat malaria. But increment in drug resistance has pushed researchers to find novel drugs to tackle drug resistance problems. The idea of using transition metal complexes with pharmacophores as ligands/ligand pendants to show enhanced antimalarial activity with a novel mechanism of action has gained significant attention recently. The advantages of metal complexes include tunable chemical/physical properties, redox activity, avoiding resistance factors, etc. Several recent reports have successfully demonstrated that the metal complexation of known organic antimalarial drugs can overcome drug resistance by showing enhanced activities than the parent drugs. This review has discussed the fruitful research works done in the past few years falling into this criterion. Based on transition metal series (3d, 4d, or 5d), the antimalarial metal complexes have been divided into three broad categories (3d, 4d, or 5d metal-based), and their activities have been compared with the similar control complexes as well as the parent drugs. Furthermore, we have also commented on the potential issues and their possible solution for translating these metal-based antimalarial complexes into the clinic.
在抗疟药物开发研究中,克服药物耐药性一直是研究人员面临的主要挑战。目前,几种药物如氯喹、甲氟喹、磺胺多辛和青蒿素被用于治疗疟疾。但是,药物耐药性的增加促使研究人员寻找新的药物来解决药物耐药性问题。最近,人们关注使用具有药效团的过渡金属配合物作为配体/配体侧链,以具有新的作用机制来显示增强的抗疟活性。金属配合物的优点包括可调节的化学/物理性质、氧化还原活性、避免耐药因素等。最近的几项报告成功证明,通过显示比母体药物更高的活性,已知有机抗疟药物的金属络合可以克服耐药性。这篇综述讨论了过去几年在这一标准下所做的富有成效的研究工作。基于过渡金属系列(3d、4d 或 5d),将抗疟金属配合物分为三类(3d、4d 或 5d 金属基),并将它们的活性与类似的对照配合物以及母体药物进行了比较。此外,我们还评论了将这些基于金属的抗疟配合物转化为临床应用的潜在问题及其可能的解决方案。