a Department of Applied Chemistry, Faculty of Science , University of Johannesburg , Johannesburg , Republic of South Africa.
b Department of Pharmacy and Pharmacology, Pharmacology Division, Faculty of Health Sciences , WITS Institute for Malaria (WRIM) , University of the Witwatersrand , Johannesburg , Republic of South Africa.
Artif Cells Nanomed Biotechnol. 2018;46(sup3):S287-S296. doi: 10.1080/21691401.2018.1491481. Epub 2019 Jan 16.
About 40% of the world's population lives in malaria zones where it presents a challenging health problem. Malaria treatment and prevention have been hindered by drug resistance. Bisphosphonates have been found to be active against Trypanosoma cruzi and Plasmodium falciparum that cause Chaga's disease and malaria respectively. However, bisphosphonates have a shortcoming of being rapidly removed from the bloodstream through the kidneys before reaching the target sites due to their low molecular weight. In the current study, increased bisphosphonates' efficacy for malaria treatment was attempted by conjugating bisphosphonates onto carbon nanospheres (CNSs). The synthesis of the target compounds was confirmed by SEM, TEM, EDX, FTIR, Raman and TGA. The target CNSs containing bisphosphonates were evaluated for antimalarial activity against a chloroquine-resistant strain of P. falciparum. From the free bisphosphonates to the conjugates, the results obtained revealed that there were improvements in percentage parasite kill (from -10.71% to 18%, -18.93% to 28.09% and 10.47% to 28.33% for alendronate, pamidronate and neridronate, respectively). The haemolysis assays revealed that the synthesized compound did not have a toxic impact on healthy red blood cells. The results indicate that bisphosphonates conjugated CNSs are said to be promising P. falciparum blood stage inhibitors.
约 40%的世界人口生活在疟疾流行地区，这对他们的健康构成了严峻挑战。抗药性的出现，阻碍了疟疾的治疗和预防。双膦酸盐已被发现对引起恰加斯病和疟疾的克氏锥虫和恶性疟原虫具有活性。然而，由于双膦酸盐的分子量较低，它们在到达靶位之前会通过肾脏迅速从血液中清除，这是其一个缺点。在当前的研究中，尝试通过将双膦酸盐偶联到碳纳米球（CNSs）上来提高双膦酸盐治疗疟疾的疗效。通过 SEM、TEM、EDX、FTIR、拉曼和 TGA 确认了目标化合物的合成。对含有双膦酸盐的目标 CNSs 进行了抗氯喹耐药恶性疟原虫的抗疟活性评价。从游离双膦酸盐到缀合物，结果表明，寄生虫杀伤率有了提高（阿仑膦酸钠从-10.71%提高到 18%，帕米膦酸从-18.93%提高到 28.09%，奈立膦酸从 10.47%提高到 28.33%）。溶血试验表明，合成的化合物对健康的红细胞没有毒性影响。结果表明，双膦酸盐偶联 CNSs 有望成为恶性疟原虫血期抑制剂。
