We previously discovered three carbazole derivatives, GJP14 (1-piperidinylmethyl-2-(1-oxo-6-methyl-1,2,3,4-tetrahydrocarbazol-9-yl)-ethan-1-ol) with anti-prion activity, GJC29 (benzylamino-3-(1,2,3,4-tetrahydrocarbazol-9-yl)-propan-2-ol) with anti-cancer activity, and THC19 (1-piperidinylmethyl-2-(1,2,3,4-tetrahydrocarnazol-9-yl)-ethan-1-ol) with anti-influenza virus activity. During optimization of GJP14 for the anti-prion activity, we discovered a compound, 1-(2,6-difluorobenzylamino)-3-(1,2,3,4-tetrahydrocarbazol-9-yl)-propan-2-ol, termed 5Y, had the most strong anti-prion activity among a series of newly synthesized derivatives. Intriguingly, we noticed that 5Y had also the most strong anti-colon cancer as well as the anti-influenza virus activities among derivatives. No significant toxicity of 5Y was observed. These results demonstrate that 5Y is a multipotent lead compound with unusually wide spectrum, and may be applicable to therapeutics targeting multiple diseases.Abbreviations: MoPrP: mouse prion protein of amino acid residues of 23-231; PrPC: cellular form of prion protein; PrPSc: scrapie form of prion protein.

中文翻译：

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发现多能分子伴侣 1-(2,6-Difluorobenzylamino)-3-(1,2,3,4-tetrahydrocarbazol-9-yl)-propan-2-ol 对朊病毒、癌症的增殖具有抑制作用以及流感病毒。

我们之前发现了三种咔唑衍生物，GJP14（1-piperdinylmethyl-2-(1-oxo-6-methyl-1,2,3,4-tetrahydrocarbazol-9-yl)-ethan-1-ol）具有抗朊病毒活性, GJC29 (benzylamino-3-(1,2,3,4-tetrahydrocarbazol-9-yl)-propan-2-ol) 具有抗癌活性，和 THC19 (1-piperidinylmethyl-2-(1,2,3 ,4-tetrahydrocarnazol-9-yl)-ethan-1-ol) 具有抗流感病毒活性。在针对抗朊病毒活性优化 GJP14 的过程中，我们发现了一种化合物，1-(2,6-difluorobenzylamino)-3-(1,2,3,4-tetrahydrocarbazol-9-yl)-propan-2-ol，被称为5Y，在一系列新合成的衍生物中具有最强的抗朊病毒活性。有趣的是，我们注意到 5Y 在衍生物中还具有最强的抗结肠癌和抗流感病毒活性。未观察到 5Y 的显着毒性。这些结果表明5Y是一种具有异常广谱的多能先导化合物，可能适用于针对多种疾病的治疗。缩写： MoPrP：氨基酸残基为23-231的小鼠朊病毒蛋白；PrPC：朊病毒蛋白的细胞形式；PrPSc：痒病形式的朊病毒蛋白。