Kos Ivan, Benov Ludmil, Spasojević Ivan, Rebouças Júlio S, Batinić-Haberle Ines
Department of Radiation Oncology, Duke University Medical School, Durham, North Carolina 27710, USA.
J Med Chem. 2009 Dec 10;52(23):7868-72. doi: 10.1021/jm900576g.
Lipophilicity/bioavailibility of Mn(III) N-alkylpyridylporphyrin-based superoxide dismutase (SOD) mimics has a major impact on their in vivo ability to suppress oxidative stress. Meta isomers are less potent SOD mimics than ortho analogues but are 10-fold more lipophilic and more planar. Enhanced lipophilicity contributes to their higher accumulation in cytosol of SOD-deficient Escherichia coli, compensating for their lower potency; consequently, both isomers exert similar-to-identical protection of SOD-deficient E. coli. Thus meta isomers may be prospective therapeutics as are ortho porphyrins.
基于Mn(III) N-烷基吡啶基卟啉的超氧化物歧化酶（SOD）模拟物的亲脂性/生物利用度对其体内抑制氧化应激的能力有重大影响。间位异构体作为SOD模拟物的效力低于邻位类似物，但亲脂性高10倍且平面性更强。增强的亲脂性有助于它们在缺乏SOD的大肠杆菌细胞质中更高的积累，弥补其较低的效力；因此，两种异构体对缺乏SOD的大肠杆菌发挥相似至相同程度的保护作用。所以间位异构体可能与邻位卟啉一样是有前景的治疗药物。
