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Synthesis, Molecular Docking, and Biological Evaluation of Novel 2-Pyrazoline Derivatives as Multifunctional Agents for the Treatment

of Alzheimer's Disease

Oya Unsal-Tana*, Tuba Tüylü Küçükkılınçb, Beyza Ayazgökb, Ayla Balkana, Keriman Ozadali-Saria

a Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ankara, TURKEY. b Hacettepe University, Faculty of Pharmacy, Department of Biochemistry, Ankara, TURKEY.

Dr. Oya Unsal Tanoyaunsal@hacettepe.edu.tr

SUPPORTING FILE

1) IR, ESI-MS, 1H and 13C- NMR SPECTRA OF THE COMPOUNDS (p 2-43)2) DOSE-RESPONSE CURVES OF 3F AND 3G (p 44-45)3) INHIBITION OF SELF-MEDIATED Aβ1–42 AGGREGATION at 10 μM (p 46)

Electronic Supplementary Material (ESI) for MedChemComm.This journal is © The Royal Society of Chemistry 2019

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1) IR, ESI-MS, 1H and 13C- NMR SPECTRA OF THE COMPOUNDS

1-(5-(4-(1H-1,2,4-Triazol-1-yl)phenyl)-3-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (3a)

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1-(5-(4-(1H-Imidazol-1-yl)phenyl)-3-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (3b)

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1-(5-(4-(1H-Benzo[d]imidazol-1-yl)phenyl)-3-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (3c)

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1-(5-(4-(4-Benzylpiperazin-1-yl)phenyl)-3-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (3d)

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1-(5-(4-(4-Benzylpiperidin-1-yl)phenyl)-3-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (3e)

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1-(5-(4-(4-Methylpiperazin-1-yl)phenyl)-3-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (3f)

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1-(5-(4-(4-Ethylpiperazin-1-yl)phenyl)-3-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (3g)

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1-(5-(4-(4-methylpiperidin-1-yl)phenyl)-3-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (3h)

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1-(5-(4-(4-Phenylpiperazin-1-yl)phenyl)-3-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (3i)

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1-(5-(4-(4-Benzylpiperazin-1-yl)phenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (3j)

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1-(5-(4-(4-Ethylpiperazin-1-yl)phenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (3k)

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2) DOSE-RESPONSE CURVES OF 3F AND 3G

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3) INHIBITION OF SELF-MEDIATED Aβ1–42 AGGREGATION at 10 μM

Table S1. In vitro effects on self-mediated Aβ1–42 aggregation at 10 μM

CompoundAβ1–42

aggregation(%)±SEM

3d 93.00±2.963e 82.21±6.69*3f 88.04±9.693g 91.42±4.013h 80.58±1.70**

Controla 100Donepezil 64.75±1.63***

a) For each assay, the control was a non-treated sample. * p < 0.05, ** p < 0.01, *** p < 0.001