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通过带有一个或两个咪唑环官能化的苯并[g]酞嗪衍生物对铁超氧化物歧化酶和克氏锥虫生长的有效抑制作用。

Efficient inhibition of iron superoxide dismutase and of Trypanosoma cruzi growth by benzo[g]phthalazine derivatives functionalized with one or two imidazole rings.

作者信息

Sanz Ana M, Gómez-Contreras Fernando, Navarro Pilar, Sánchez-Moreno Manuel, Boutaleb-Charki Samira, Campuzano Jose, Pardo Mercedes, Osuna Antonio, Cano Carmen, Yunta María J R, Campayo Lucrecia

机构信息

Departamento de Química Orgánica I, Facultad de Química, Universidad Complutense, Madrid, Spain.

出版信息

J Med Chem. 2008 Mar 27;51(6):1962-6. doi: 10.1021/jm701179m. Epub 2008 Feb 23.

Abstract

The synthesis and trypanosomatic behavior of a new series of 1,4-bis(alkylamino)benzo[g]phthalazines 1- 4 containing the biologically significant imidazole ring are reported. In vitro antiparasitic activity against Trypanosoma cruzi epimastigotes is remarkable, especially for compound 2, whereas toxicity against Vero cells is very low. Conversion of epimastigotes to metacyclic forms in the presence of the tested compounds causes significant decreases in the amastigote and trypomastigote numbers. Fe-SOD inhibition is noteworthy, whereas effect on human Cu/Zn-SOD is negligible.

摘要

报道了一系列含有具有生物学意义的咪唑环的新型1,4-双(烷基氨基)苯并[g]酞嗪1-4的合成及其对锥虫的作用。体外对克氏锥虫前鞭毛体的抗寄生虫活性显著,尤其是化合物2,而对Vero细胞的毒性非常低。在受试化合物存在下,前鞭毛体向循环后期形式的转化导致无鞭毛体和锥鞭毛体数量显著减少。值得注意的是对铁超氧化物歧化酶(Fe-SOD)的抑制作用,而对人铜/锌超氧化物歧化酶(Cu/Zn-SOD)的影响可忽略不计。

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