过氧化物键的化学稳定性使得强效四氧烷抗疟药能够进行多样化合成。
Chemical stability of the peroxide bond enables diversified synthesis of potent tetraoxane antimalarials.
作者信息
Opsenica Igor, Opsenica Dejan, Smith Kirsten S, Milhous Wilbur K, Solaja Bogdan A
机构信息
Institute of Chemistry, Technology and Metallurgy, Belgrade, Serbia.
出版信息
J Med Chem. 2008 Apr 10;51(7):2261-6. doi: 10.1021/jm701417a. Epub 2008 Mar 11.
Of 17 prepared 1,2,4,5-tetraoxacyclohexanes stable to reductive and acidic conditions, 3 of them were more active than artemisinin against CQ and MFQ resistant strain TM91C235 and all compounds were more active in vitro against W2 than against D6 strain. In vivo, amines 10 and 11a cured all mice at higher doses with MCD < or = 37.5 (mg/kg)/day. Triol 13 was exceptionally active against melanoma (LOX IMVI) and ovarian cancer (IGROV1), both with LC 50 = 60 nM.
在17种对还原和酸性条件稳定的1,2,4,5 - 四氧杂环己烷中，其中3种对氯喹和甲氟喹耐药菌株TM91C235的活性比青蒿素更高，并且所有化合物在体外对W2菌株的活性比对D6菌株更高。在体内，胺10和11a在较高剂量下（MCD≤37.5（mg/kg）/天）可治愈所有小鼠。三醇13对黑色素瘤（LOX IMVI）和卵巢癌（IGROV1）具有异常高的活性，两者的半数致死浓度（LC50）均为60 nM。
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