Srivastava Kumkum, Agarwal Pooja, Soni Awakash, Puri S K
Parasitology Division, CSIR-Central Drug Research Institute, Sect-10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, India.
Academy of Scientific and Innovative Research, New Delhi, India.
Parasitol Res. 2017 Jul;116(7):1849-1854. doi: 10.1007/s00436-017-5455-5. Epub 2017 May 13.
Present efforts have been made to establish a correlation between in vitro and in vivo antimalarial activity using MIC, IC and IC values against CQ-sensitive (3D7) and CQ-resistant (K1) strains of Plasmodium falciparum and in vivo activity against Plasmodium yoelii. The method of discriminant function analysis (DFA) was applied to analyze the data. It was observed that in vitro IC values against both 3D7 and K1 strains (p < 0.001) have strong correlation with in vivo curative activity. The respective IC and IC values of compounds, which cured mice (i.e., animals did not show recrudescence of parasitemia even after 60 days posttreatment), ranged between 3 and 14 nM and 14 and 186 nM against 3D7 and between 9 and 65 nM and 24 and 359 nM against the K1 strain of P. falciparum. Whereas the IC and IC values of compounds which exhibited in vivo suppressive activity in mice ranged between 10 and 307 nm and 61 and >965 nM, respectively, against 3D7 and 75 and >806 nm and 241 and >1232 nM against the K1 strain of P. falciparum. The findings suggest that IC values against both 3D7 and K1 strains (p < 0.02) are the main contributors for the prediction of in vivo curative activity of a new molecule. Apart from this, a reasonable correlation between MIC and IC values of compounds has also been established.
目前已开展相关工作，利用针对恶性疟原虫氯喹敏感株（3D7）和氯喹耐药株（K1）的最低抑菌浓度（MIC）、半数抑制浓度（IC）和IC值，以及对约氏疟原虫的体内活性，建立体外和体内抗疟活性之间的相关性。应用判别函数分析（DFA）方法对数据进行分析。结果发现，针对3D7和K1株的体外IC值（p < 0.001）与体内治疗活性具有很强的相关性。治愈小鼠（即动物在治疗后60天即使未出现寄生虫血症复发）的化合物，其针对3D7株的IC值和IC值分别在3至14 nM和14至186 nM之间，针对恶性疟原虫K1株的IC值和IC值分别在9至65 nM和24至359 nM之间。而在小鼠中表现出体内抑制活性的化合物，其针对3D7株的IC值和IC值分别在10至307 nM和61至>965 nM之间，针对恶性疟原虫K1株的IC值和IC值分别在75至>806 nM和241至>1232 nM之间。研究结果表明，针对3D7和K1株的IC值（p < 0.02）是预测新分子体内治疗活性的主要因素。除此之外，还建立了化合物MIC值和IC值之间的合理相关性。
