Discovery of a multipotent chaperone, 1-(2,6-Difluorobenzylamino)-3-(1,2,3,4-tetrahydrocarbazol-9-yl)-propan-2-ol with the inhibitory effects on the proliferation of prion, cancer as well as influenza virus

• Published in: Prion 2020-01, Vol.14 (1), p.42-46
• Main Authors: Yamashita, Satoshi, Honda, Ryo, Fukuoka, Mayuko, Kimura, Tsutomu, Hosokawa-Muto, Junji, Kuwata, Kazuo
• Format: Article
• Language: English
• Subjects: activation free energy; anti-viral agent; cancer; carbazol; Chaperone; free energy; influenza virus; multipotent; prion; Short Communication; stabilization
• ISSN: 1933-6896; 1933-690X
• DOI: 10.1080/19336896.2020.1714372

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; PrP C : cellular form of prion protein; PrP Sc : scrapie form of prion protein