Ariefta Nanang Rudianto, Pagmadulam Baldorj, Nihei Coh-Ichi, Nishikawa Yoshifumi
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro 080-8555, Japan.
Laboratory of Microbial Synthesis, Institute of General and Experimental Biology, Mongolian Academy of Sciences, Ulaanbaatar Peace Avenue-54b, Ulaanbaatar 13330, Mongolia.
Pharmaceutics. 2022 Feb 28;14(3):544. doi: 10.3390/pharmaceutics14030544.
The emerging spread of drug-resistant malaria parasites highlights the need for new antimalarial agents. This study evaluated the growth-inhibitory effects of sparsomycin (Sm), a peptidyl transferase inhibitor, against 3D7 (chloroquine-sensitive strain), K1 (resistant to multiple drugs, including chloroquine), 17XNL (cause of uncomplicated rodent malaria) and ANKA (cause of complicated rodent malaria). Using a fluorescence-based assay, we found that Sm exhibited half-maximal inhibitory concentrations (IC) of 12.07 and 25.43 nM against 3D7 and K1, respectively. In vitro treatment of 3D7 with Sm at 10 or 50 nM induced morphological alteration, blocked parasites in the ring state and prevented erythrocyte reinvasion, even after removal of the compound. In mice infected with 17XNL, the administration of 100 μg/kg Sm for 7 days did not affect parasitemia. Meanwhile, treatment with 300 μg/kg Sm resulted in a significantly lower parasitemia peak (18.85%) than that observed in the control group (40.13%). In mice infected with ANKA, both four and seven doses of Sm (300 μg/kg) prolonged survival by 33.33%. Our results indicate that Sm has potential antiplasmodial activities in vitro and in vivo, warranting its further development as an alternative treatment for malaria.
耐药疟原虫的不断传播凸显了新型抗疟药物的必要性。本研究评估了肽基转移酶抑制剂稀疏霉素（Sm）对3D7（氯喹敏感株）、K1（对包括氯喹在内的多种药物耐药）、17XNL（引起非复杂性啮齿动物疟疾）和ANKA（引起复杂性啮齿动物疟疾）的生长抑制作用。通过基于荧光的检测方法，我们发现Sm对3D7和K1的半数最大抑制浓度（IC）分别为12.07 nM和25.43 nM。用10或50 nM的Sm对3D7进行体外处理会诱导形态改变，使疟原虫停滞在环状阶段，并阻止其再次侵入红细胞，即使在去除该化合物后也是如此。在感染17XNL的小鼠中，给予100 μg/kg的Sm持续7天对疟原虫血症没有影响。同时，用300 μg/kg的Sm治疗导致疟原虫血症峰值（18.85%）显著低于对照组（40.13%）。在感染ANKA的小鼠中，四剂和七剂Sm（300 μg/kg）均使生存期延长了33.33%。我们的结果表明，Sm在体外和体内均具有潜在的抗疟原虫活性，值得进一步开发作为疟疾的替代治疗方法。
