tetano
Editor, Senior Moderator
Prion. 2020 Dec;14(1):42-46. doi: 10.1080/19336896.2020.1714372. [h=1]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.[/h]
Yamashita S[SUP]1[/SUP], Honda R[SUP]1[/SUP], Fukuoka M[SUP]1[/SUP], Kimura T[SUP]2[/SUP], Hosokawa-Muto J[SUP]3[/SUP], Kuwata K[SUP]1,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]C[/SUP]: cellular form of prion protein; PrP[SUP]Sc[/SUP]: scrapie form of prion protein.
[h=4]KEYWORDS:[/h] Chaperone; activation free energy; anti-viral agent; cancer; carbazol; free energy; influenza virus; multipotent; prion; stabilization
PMID: 31971853 DOI: 10.1080/19336896.2020.1714372
Yamashita S[SUP]1[/SUP], Honda R[SUP]1[/SUP], Fukuoka M[SUP]1[/SUP], Kimura T[SUP]2[/SUP], Hosokawa-Muto J[SUP]3[/SUP], Kuwata K[SUP]1,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]C[/SUP]: cellular form of prion protein; PrP[SUP]Sc[/SUP]: scrapie form of prion protein.
[h=4]KEYWORDS:[/h] Chaperone; activation free energy; anti-viral agent; cancer; carbazol; free energy; influenza virus; multipotent; prion; stabilization
PMID: 31971853 DOI: 10.1080/19336896.2020.1714372