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目的观察4种胆碱衍生物对恶性疟原虫3D7株的抑制作用。方法用二甲基亚砜(DMSO)溶解MD(N-十二烷基-N-(2-羟乙基)-N,N-二甲基溴化铵)、ED(N-十二烷基-N-(2-羟乙基)-N,N-二乙基溴化铵)、MT(N-十四烷基-N-(2-羟乙基)-N,N-二甲基溴化铵)和ET(N-十四烷基-N-(2-羟乙基)-N,N-二乙基溴化铵)等4种胆碱衍生物,制成10倍浓度梯度(1~105μmol/L)的溶液后,分别用RPMI 1640培养基稀释1 000倍。稀释红细胞,使疟原虫感染率为0.3%~0.5%,并用培养基将红细胞压积调至2%。测定板每孔加入20μl含药培养液和80μl恶性疟原虫培养物,用SYBR GreenⅠ法测定胆碱衍生物对疟原虫增殖的抑制作用,并以青蒿素为阳性对照,计算其50%抑制浓度(IC50)。结果青蒿素、MD、ED、MT和ET对恶性疟原虫的抑制作用均随浓度的升高而增强,表现出不同程度的剂量依赖性。MD浓度>103nmol/L时,对恶性疟原虫的抑制率显著增加。ED和ET在高浓度(>104nmol/L)时抑制显著,抑制率均>95%。MD、ED、MT和ET的IC50值分别为1 620、33.9、116和68.9 nmol/L,均高于青蒿素(5.7 nmol/L,P<0.05)。结论 4种胆碱衍生物均有一定的体外抗恶性疟原虫活性,但活性低于青蒿素。4种衍生物中,ED对恶性疟原虫3D7株的抑制作用最强。
Objective To observe the inhibitory effects of four choline derivatives on Plasmodium falciparum 3D7 strain. Methods MD (N-dodecyl-N- (2-hydroxyethyl) -N, N-dimethyl ammonium bromide), ED (N-dodecyl N- (2-hydroxyethyl) -N, N- diethyl ammonium bromide), MT (N-tetradecyl-N- Ammonium chloride) and ET (N-tetradecyl-N- (2-hydroxyethyl) -N, N- diethyl ammonium bromide) and other four kinds of choline derivatives made of 10 times the concentration gradient ~ 105μmol / L) solution, respectively, diluted 1 000 times with RPMI 1640 medium. Dilute red blood cells, so that the infection rate of 0.3% to 0.5% of malaria, and the medium hematocrit adjusted to 2%. Each well of the assay plate was filled with 20 μl of the drug-containing culture medium and 80 μl of the culture of P. falciparum. The inhibitory effect of the choline derivatives on the growth of the malaria parasite was determined by the SYBR GreenⅠmethod. The concentration of 50% inhibition was calculated using artemisinin as a positive control (IC50). Results The inhibitory effects of artemisinin, MD, ED, MT and ET on Plasmodium falciparum all increased with increasing concentration, showing different degrees of dose dependence. MD concentration> 103nmol / L, the inhibition of Plasmodium falciparum significantly increased. ED and ET inhibited significantly at high concentration (> 104nmol / L), the inhibition rates were> 95%. The IC50 values of MD, ED, MT and ET were 1 620, 33.9, 116 and 68.9 nmol / L, respectively, higher than that of artemisinin (5.7 nmol / L, P <0.05). Conclusion All four choline derivatives have some anti-Plasmodium falciparum activity in vitro, but their activity is lower than that of artemisinin. Of the four derivatives, ED had the strongest inhibitory effect on Plasmodium falciparum 3D7 strain.