ars.els-cdn.com file · Web viewwas added after 2 days without treatment. Then, the cells were...
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Design and synthesis of new theranostic agents for near-infrared imaging of -amyloid plaques and inhibition of -amyloid aggregation in Alzheimer's disease Pascal Dao a , Feifei Ye a , Zhi Yun Du a , Qian Chen a , Kun Zhang a , Chang Zhi Dong a,c , Bernard Meunier a,d , Huixiong Chen a,b,* a Faculty of Light Industry and Chemical Engineering, Guang Dong University of Technology, Guang Dong, 510006, China; b CNRS, UMR8601, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CBNIT, Université Paris Descartes, PRES Sorbonne Paris Cité, UFR Biomédicale, 75006 Paris, France; c Université Paris Diderot, Sorbonne Paris Cité, ITODYS, UMR 7086 CNRS, 75013 Paris, France; d Laboratoire de Chimie de Coordination du CNRS, 205 Route de Narbonne, 31077 Toulouse Cedex, France. *Corresponding author: Huixiong Chen, UFR Biomédicale, Université Paris Descartes, Tel: (+33)142864085, Email: [email protected] Content Page Fluorescence staining of 5a1 and 6a on brain slices of cortex regions of a double Tg mouse (10 months, Figure S1). S2 Inhibition of self aggregation of Aβ by 5a1 using fluorescence microscopy. S3 NMR Spectra S4 S1
Transcript of ars.els-cdn.com file · Web viewwas added after 2 days without treatment. Then, the cells were...
Design and synthesis of new theranostic agents for near-infrared imaging of -amyloid plaques and inhibition of -amyloid aggregation in Alzheimer's disease
Pascal Daoa, Feifei Yea, Zhi Yun Dua, Qian Chena, Kun Zhanga, Chang Zhi Donga,c, Bernard
Meuniera,d, Huixiong Chena,b,*
aFaculty of Light Industry and Chemical Engineering, Guang Dong University of Technology, Guang Dong, 510006, China; bCNRS, UMR8601, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CBNIT, Université Paris Descartes, PRES Sorbonne Paris Cité, UFR Biomédicale, 75006 Paris, France; cUniversité Paris Diderot, Sorbonne Paris Cité, ITODYS, UMR 7086 CNRS, 75013 Paris, France; dLaboratoire de Chimie de Coordination du CNRS, 205 Route de Narbonne, 31077 Toulouse Cedex, France.
*Corresponding author: Huixiong Chen, UFR Biomédicale, Université Paris Descartes, Tel: (+33)142864085,
Email: [email protected]
Content Page
Fluorescence staining of 5a1 and 6a on brain slices of cortex regions of a double Tg mouse (10 months, Figure S1). S2Inhibition of self aggregation of Aβ by 5a1 using fluorescence microscopy. S3NMR Spectra S4
S1
Figure S1. Fluorescence staining of 5a1 and 6a on brain slices in the cerebral cortex from a double Tg
mouse (5a1: G and H, magnification: 5X; 6a: K and L, magnification: 5X). Adjacent slices from Tg
mouse were stained with ThT (C and D, magnification: 5X). Brain slices from wild-type control
mouse (C57BL/6) was also used in the same conditions with 5a1 (E and F), 6a (I and J) and ThT (A
and B).
S2
Figure S2. Inhibition of intracellular self-aggregation of Aβ in SH-SY5Y cells. (A) Cells grown in the
presence of Aβ monomer and 5a1 (1 µM) for 2 days, then imaged using fluorescence microscopy. For
control experiment, 5a1 was added after 2 days without treatment. (B) The histogram represents the
fluorescence intensity measured using ImageJ software. Error bars, s.e.m from three independent
experiments and four random fields.
Inhibition of intracellular self-aggregation of Aβ in SH-SY5Y cells.
SHSY5Y cells were incubated with 250 nM of Aβ monomer and 5a1 (1 µM) for 48 h.
For control experiment, 5a1 was added after 2 days without treatment. Then, the cells were imaged
using the fluorescence microscope. Four images from random regions of the culture dish were
analyzed and the fluorescence intensity was measured using ImageJ software.
S3
Figure S3: 1H NMR (CDCl3, 400 MHz) and 13C NMR (CDCl3, 400 MHz) of ethyl 2-((Z)-5-((E)-3-(10-methyl-10H-phenothiazin-3-yl)allylidene)-4-oxo-2-thioxothiazolidin-3-yl)acetate (5a1)
S4
Figure S4: 1H NMR (CDCl3, 400 MHz) and 13C NMR (CDCl3, 400 MHz) of tert-butyl 2-((Z)-5-((E)-3-(10-methyl-10H-phenothiazin-3-yl)allylidene)-4-oxo-2-thioxothiazolidin-3-yl)acetate (5a2)
S5
Figure S5: 1H NMR (CDCl3, 400 MHz) and 13C NMR (CDCl3, 400 MHz) of tert-butyl 2-((Z)-5-((E)-3-(8-chloro-10-methyl-10H-phenothiazin-3-yl)allylidene)-4-oxo-2-thioxothiazolidin-3-yl)acetate (5b2)
S6
Figure S6: 1H NMR (CDCl3, 400 MHz) and 13C NMR (CDCl3, 400 MHz) of tert-butyl 3-((Z)-5-((E)-3-(10-methyl-10H-phenothiazin-3-yl)allylidene)-4-oxo-2-thioxothiazolidin-3-yl)propanoate (7)
S7
Figure S7: 1H NMR (CDCl3, 400 MHz) and 13C NMR (CDCl3, 400 MHz) of ethyl 2-((Z)-5-((2E,4E)-5-(10-methyl-10H-phenothiazin-3-yl)penta-2,4-dien-1-ylidene)-4-oxo-2-thioxothiazolidin-3-yl)acetate (9a1)
S8
Figure S8: 1H NMR (CDCl3, 400 MHz) and 13C NMR (CDCl3, 400 MHz) of tert-butyl 2-((Z)-5-((2E,4E)-5-(10-methyl-10H-phenothiazin-3-yl)penta-2,4-dien-1-ylidene)-4-oxo-2-thioxothiazolidin-3-yl)acetate (9a2)
S9
Figure S9: 1H NMR (CDCl3, 400 MHz) and 13C NMR (CDCl3, 400 MHz) of tert-butyl 3-((Z)-5-((2E,4E)-5-(10-methyl-10H-phenothiazin-3-yl)penta-2,4-dien-1-ylidene)-4-oxo-2-thioxothiazolidin-3-yl)propanoate (10)
S10
Figure S10: 1H NMR (DMSO, 400 MHz) and 13C NMR (DMSO, 400 MHz) of 2-((Z)-5-((E)-3-(10-methyl-10H-phenothiazin-3-yl)allylidene)-4-oxo-2-thioxothiazolidin-3-yl)acetic acid (6a)
S11
Figure S11: 1H NMR (CD)3CO, 400 MHz) and 13C NMR (DMSO, 400 MHz) of 2-((Z)-5-((E)-3-(8-chloro-10-methyl-10H-phenothiazin-3-yl)allylidene)-4-oxo-2-thioxothiazolidin-3-yl)acetic acid (6b)
S12
Figure S12: 1H NMR (DMSO, 400 MHz) and 13C NMR (DMSO, 400 MHz) of 3-((Z)-5-((E)-3-(10-methyl-10H-phenothiazin-3-yl)allylidene)-4-oxo-2-thioxothiazolidin-3-yl)propanoicacid (8)
S13
Figure S13: 1H NMR (DMSO, 400 MHz) and 13C NMR (DMSO, 400 MHz) of 2-((Z)-5-((2E,4E)-5-(10-methyl-10H-phenothiazin-3-yl)penta-2,4-dien-1-ylidene)-4-oxo-2-thioxothiazolidin-3-yl)acetic acid (11)
S14
Figure S14: 1H NMR (DMSO, 400 MHz) and 13C NMR (DMSO, 400 MHz) of 3-((Z)-5-((2E,4E)-5-(10-methyl-10H-phenothiazin-3-yl)penta-2,4-dien-1-ylidene)-4-oxo-2-thioxothiazolidin-3-yl)propanoic acid (12)
S15
