Chirawurah Jersley D, Ansah Felix, Blankson Samuel, Adikah Bridget, Yeboah Silas Nkansah, Amenga-Etego Lucas, Awandare Gordon A, Aniweh Yaw
West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Accra, Ghana.
Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana.
Sci Rep. 2025 Jan 9;15(1):1469. doi: 10.1038/s41598-025-85643-6.
Gossypol has demonstrated significant antimalarial activity against chloroquine-resistant and susceptible Plasmodium falciparum parasites. However, data on its potency in clinical isolates of P. falciparum remains limited. This study aimed to assess the potency of gossypol against six laboratory strains and twenty-one clinical isolates of P. falciparum using optimized growth inhibition assays. Additionally, parasites with reduced susceptibility to gossypol were selected using the P. falciparum Dd2 background (Dd2_3.5 µM) and tested for cross-resistance to chloroquine, dihydroartemisinin (DHA), and three Malaria box compounds (MMV006087, MMV085203, and MMV008956). On average, gossypol was found to be twice as potent against the laboratory strains compared to the clinical isolates, with IC₅₀ values of 6.490 µM and 11.670 µM, respectively. Notably, Dd2_3.5 µM parasites displayed increased sensitivity after three months of exposure but developed decreased susceptibility after six months. Importantly, these gossypol-tolerant parasites showed no cross-resistance to chloroquine, DHA, or the three Malaria box compounds. These findings suggest that gossypol is effective against P. falciparum and holds potential as part of combination therapy with existing antimalarials. Furthermore, these results may support the identification of new antimalarial agents that are effective against drug-resistant malaria parasites.
棉酚已显示出对氯喹耐药和敏感的恶性疟原虫具有显著的抗疟活性。然而，关于其对恶性疟原虫临床分离株效力的数据仍然有限。本研究旨在使用优化的生长抑制试验评估棉酚对六种实验室菌株和二十一种恶性疟原虫临床分离株的效力。此外，使用恶性疟原虫Dd2背景（Dd2_3.5 μM）选择对棉酚敏感性降低的寄生虫，并测试其对氯喹、双氢青蒿素（DHA）和三种疟疾盒化合物（MMV006087、MMV085203和MMV008956）的交叉耐药性。平均而言，发现棉酚对实验室菌株的效力是临床分离株的两倍，IC₅₀值分别为6.490 μM和11.670 μM。值得注意的是，Dd2_3.5 μM寄生虫在暴露三个月后敏感性增加，但在六个月后敏感性降低。重要的是，这些耐棉酚的寄生虫对氯喹、DHA或三种疟疾盒化合物没有交叉耐药性。这些发现表明，棉酚对恶性疟原虫有效，作为与现有抗疟药联合治疗的一部分具有潜力。此外，这些结果可能支持鉴定对耐药疟原虫有效的新型抗疟药。
