Sharma Supriya, Kaitholia Kamlesh, Mishra Neelima, Srivastava Bina, Pillai C R, Valecha Neena, Anvikar Anupkumar R
Department of Epidemiology and Clinical Research, National Institute of Malaria Research, Sector-8, New Delhi, India.
Indian J Med Microbiol. 2016 Oct-Dec;34(4):509-512. doi: 10.4103/0255-0857.195365.
Artemisinin (ART) and its derivatives form the mainstay of antimalarial therapy. Emergence of resistance to them poses a potential threat to future malaria control and elimination on a global level. It is important to know the mechanism of action of drug and development of drug resistance. We put forwards probable correlation between the mode of action of chloroquine (CQ) and ART. Modified trophozoite maturation inhibition assay, WHO Mark III assay and molecular marker study for CQ resistance at K76T codon in Plasmodium falciparum CQ-resistant transporter gene were carried out on cultured P. falciparum. On comparing trophozoite and schizont growth for both CQ-sensitive (MRC-2) and CQ-resistant (RKL-9) culture isolates, it was observed that the clearance of trophozoites and schizonts was similar with both drugs. The experiment supports that CQ interferes with heme detoxification pathway in food vacuoles of parasite, and this may be correlated as one of the plausible mechanisms of ART.
青蒿素(ART)及其衍生物是抗疟治疗的主要药物。对它们产生耐药性对全球未来的疟疾控制和消除构成了潜在威胁。了解药物的作用机制和耐药性的发展很重要。我们提出了氯喹(CQ)和ART作用方式之间可能存在的关联。对培养的恶性疟原虫进行了改良的滋养体成熟抑制试验、世卫组织Mark III试验以及针对恶性疟原虫CQ耐药转运蛋白基因中K76T密码子的CQ耐药分子标记研究。在比较CQ敏感(MRC-2)和CQ耐药(RKL-9)培养分离株的滋养体和裂殖体生长情况时,发现两种药物对滋养体和裂殖体的清除效果相似。该实验支持CQ干扰寄生虫食物泡中的血红素解毒途径,这可能是ART的一种合理作用机制之一。