Department of Chemistry, Gobardanga Hindu College, North 24 Parganas, West Bengal 743273, India.
Biochem Pharmacol. 2023 Dec;218:115927. doi: 10.1016/j.bcp.2023.115927. Epub 2023 Nov 20.
The search for effective antimalarial agents remains a critical priority because malaria is widely spread and drug-resistant strains are becoming more prevalent. In this review, a variety of small molecules capable of modulating redox processes were showcased for their potential as antimalarial agents. The compounds were designed to target the redox balance of Plasmodium parasites, which has a pivotal function in their ability to survive and multiply within the host organism. A thorough screening method was utilized to assess the effectiveness of these compounds against both drug-sensitive and drug-resistant strains of Plasmodium falciparum, the malaria-causing parasite. The results revealed that several of the tested compounds exhibited significant effectiveness against malaria, displaying IC values at a low micromolar range. Furthermore, these compounds displayed promising selectivity for the parasite, as they exhibited low cytotoxicity towards mammalian cells. Thorough mechanistic studies were undertaken to clarify how the active compounds exert their mode of action. The findings revealed that these compounds disrupted the parasites' redox balance, causing oxidative stress and interfering with essential cellular functions. Additionally, the compounds showed synergistic effects when combined with existing antimalarial drugs, suggesting their potential for combination therapies to combat drug resistance. Overall, this study highlights the potential of redox-modulating small molecules as effective antimalarial agents. The identified compounds demonstrate promising antimalarial activity, and their mechanism of action offers insights into targeting the redox balance of Plasmodium parasites. Further optimization and preclinical studies are warranted to determine their efficacy, safety, and potential for clinical development as novel antimalarial therapeutics.
寻找有效的抗疟药物仍然是当务之急，因为疟疾广泛传播，并且耐药菌株越来越普遍。在这篇综述中，展示了多种能够调节氧化还原过程的小分子，因为它们具有作为抗疟药物的潜力。这些化合物旨在针对疟原虫的氧化还原平衡，这对于寄生虫在宿主生物体内生存和繁殖的能力至关重要。我们采用了一种彻底的筛选方法来评估这些化合物对敏感和耐药疟原虫（引起疟疾的寄生虫）菌株的有效性。结果表明，几种测试化合物对疟疾具有显著的疗效，对疟原虫的 IC 值处于低微摩尔范围内。此外，这些化合物对哺乳动物细胞表现出低细胞毒性，显示出对寄生虫的良好选择性。我们进行了深入的机制研究，以阐明活性化合物的作用方式。研究结果表明，这些化合物破坏了寄生虫的氧化还原平衡，导致氧化应激并干扰了重要的细胞功能。此外，这些化合物与现有的抗疟药物联合使用时表现出协同作用，表明它们在治疗耐药性方面具有联合治疗的潜力。总的来说，这项研究强调了氧化还原调节小分子作为有效抗疟药物的潜力。鉴定出的化合物表现出有希望的抗疟活性，其作用机制为靶向疟原虫的氧化还原平衡提供了思路。需要进一步的优化和临床前研究来确定它们的疗效、安全性以及作为新型抗疟治疗药物的临床开发潜力。
