Chiou G C, Xuan B, Liu Q, Yamasaki T, Okawara T
Institute of Ocular Pharmacology and Department of Medical Pharmacology and Toxicology, Texas A & M University System Health Science Center, College of Medicine, College Station 77843-1114, USA.
J Ocul Pharmacol Ther. 2000 Oct;16(5):407-18. doi: 10.1089/jop.2000.16.407.
Interleukin-1 (IL-1) is known to trigger induction of inducible nitric oxide synthase (iNOS) to persistently mass produce nitric oxide (NO) to induce various diseases such as cancer, inflammation, Alzheimer's disease and eye diseases, including uveitis, retinopathy, age-related macular degeneration, glaucoma and myopia. Therefore, IL-1 blockers could become an important class of drugs to fight numerous diseases. Among the many compounds studied so far, 1-methyl hydrazino analogs are among the most promising agents to be developed. A minor structural change of 1-methyl hydrazino group into 1-methyl thiosemicarbazido group enhanced their anti-inflammatory activity but reduced their antiproliferation activity on corneal fibroblast cell growth.
白细胞介素-1(IL-1)已知可触发诱导型一氧化氮合酶(iNOS)的诱导,从而持续大量产生一氧化氮(NO),进而引发各种疾病,如癌症、炎症、阿尔茨海默病以及眼部疾病,包括葡萄膜炎、视网膜病变、年龄相关性黄斑变性、青光眼和近视。因此,IL-1阻断剂可能成为对抗众多疾病的一类重要药物。在迄今为止研究的众多化合物中,1-甲基肼类似物是最有开发前景的药物之一。将1-甲基肼基团进行微小的结构改变为1-甲基硫代氨基脲基团,增强了它们的抗炎活性,但降低了它们对角膜成纤维细胞生长的抗增殖活性。