• No results found

Supporting Information Molecular modelling, synthesis, and biological evaluations of a 3,5-disubstituted isoxazole fatty acid analogue as a

N/A
N/A
Info
Nedlasting
Protected

Academic year: 2022

Share "Supporting Information Molecular modelling, synthesis, and biological evaluations of a 3,5-disubstituted isoxazole fatty acid analogue as a"

Copied!
7
0
0

Laster.... (Se fulltekst nå)

Last ned nå ( 7 sider )

Fulltekst

(1)

Supporting Information

Molecular modelling, synthesis, and biological evaluations of a 3,5-disubstituted isoxazole fatty acid analogue as a PPARα -selective agonist

Henriette Arnesen

1

, Nadia Alazraq

1

, Jørn E. Tungen

2

, Helen Södling

1

, Jason

Matthews

1

, Steinar M. Paulsen

3

, Hilde Nebb

1

, Ingebrigt Sylte

4

, Trond V. Hansen

2

and Thomas Sæther

1,5

1

Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, N- 0317 Oslo, Norway

2

Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, N-0316 Oslo, Norway

3

MabCent-SFI, UiT – The Arctic University of Norway, N-9037 Tromsø, Norway

4

Department of Medical Biology, Faculty of Health Sciences, UiT – The Arctic University of Norway, N-9037 Tromsø, Norway

5

Department of Molecular Medicine, Institute of Basic Medical Sciences, University of

Oslo, N-0317 Oslo, Norway

(2)

-1.0 -0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5

9.0 f1 (ppm)

-1000 0 1000 2000 3000 4000 5000 6000 7000 8000 9000 10000 11000 12000 13000 14000 15000

3.04

8.04

1.90

1.98

2.99

1.00 0.870.880.901.251.261.281.281.291.301.301.311.321.331.341.341.351.361.361.371.681.701.711.731.752.782.802.823.966.41

Fig S1.

1

H NMR spectrum of compound 6 in CDCl

3

(400 MHz)

-10 0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200

210 f1 (ppm)

-100 0 100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 1400 1500 1600 1700 1800 1900 2000

14.04

22.5826.7027.3728.8328.9231.62

52.75

101.40

156.04160.71

175.85

Fig S2.

13

C NMR spectrum of compound 6 in CDCl

3

(101 MHz)

O N O

OMe

O N O

OMe

(3)

-1.0 -0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 11.5

12.0 f1 (ppm)

-100 0 100 200 300 400 500 600 700 800 900 1000

3.12

8.36

2.05

2.00

0.95

0.92 0.860.880.901.261.281.281.301.311.331.341.361.671.701.721.751.772.792.812.846.3710.12

Fig S3.

1

H NMR spectrum of compound 7 in CDCl

3

(300 MHz)

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000 11000 12000 13000 14000 15000 16000 17000 18000 19000 20000 21000 22000

14.19

22.7226.8427.4928.9629.0731.76

98.07

162.30

176.28

185.26

O N

O O

N O

(4)

0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5

11.0 f1 (ppm)

0 100 200 300 400 500 600 700 800 900 1000

3.09

8.62

2.122.07

2.092.002.02

1.000.99

1.00

0.90 0.850.880.901.261.261.271.281.291.311.311.321.321.331.341.351.641.671.691.711.741.771.801.821.851.872.402.422.452.472.472.492.502.522.522.542.552.702.722.755.875.895.915.925.935.965.996.266.276.286.306.316.319.15

Fig S5.

1

H NMR spectrum of compound 9 in CDCl

3

(300 MHz)

-10 0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200

210 f1 (ppm)

-1000 0 1000 2000 3000 4000 5000 6000 7000 8000 9000 10000 11000 12000 13000 14000 15000

14.2122.7524.2626.7927.6528.9229.0229.2031.8133.47

101.27

117.89

137.59

159.86

173.53

179.25

Fig S6.

13

C NMR spectrum of compound 9 in CDCl

3

(101 MHz)

O

N OH

O

O

N OH

O

(5)

-0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 11.5

12.0 f1 (ppm)

-1000 0 1000 2000 3000 4000 5000 6000 7000 8000 9000 10000 11000 12000 13000

3.02

10.00

5.91

2.03

3.94

1.00

1.15 0.860.870.891.261.271.271.281.291.301.301.311.311.321.331.341.341.351.411.421.431.631.641.651.661.671.681.691.712.332.352.372.602.622.642.662.682.705.80

10.12

Fig S7.

1

H NMR spectrum of compound 1 in CDCl

3

(400 MHz)

0 1000 2000 3000 4000 5000 6000 7000 8000 9000 10000 11000 12000 13000 14000

14.1922.7324.4625.9826.8527.6328.0328.7029.0229.1931.7933.97

100.36

163.82

173.64

179.59

O N

OH O

O N

OH O

(6)

Fig S9. HRMS ESI

+

spectrum of compound 1 in CH

2

Cl

2

/MeOH (95:5)

O N

OH O

(7)

Table S1. Human SYBR green RT-qPCR primers

Name Full Name Accession Number 5' – 3' Sequence

TBP-F TATA box binding protein, transcript variant 1 NM_003194.4 TTGTACCGCAGCTGCAAAAT TBP-R TATA box binding protein, transcript variant 1 NM_003194.4 TATATTCGGCGTTTCGGGCA CPT1A-F Carnitine palmitoyltransferase 1A (liver) NM_001876.3 CAGGAGACAGAGTTCCCTGG CPT1A-R Carnitine palmitoyltransferase 1A (liver) NM_001876.3 TCTAACGTCACGAAGAACGCT PPARA-F Peroxisome proliferator-activated receptor alpha NM_001001928.2 TCGGCGAGGATAGTTCTGGA PPARA-R Peroxisome proliferator-activated receptor alpha NM_001001928.2 TGAAAGCGTGTCCGTGATGA

SCD-F Stearoyl-CoA desaturas NM_005063.4 ACACCCAGCTGTCAAAGAGA

SCD-R Stearoyl-CoA desaturase NM_005063.4 GCCAGGTTTGTAGTACCTCCTC

SREBF1-F Sterol regulatory element binding transcription factor 1 NM_001005291.2 CCGCTCCTCCATCAATGACA SREBF1-R Sterol regulatory element binding transcription factor 1 NM_001005291.2 GCTGTGTTGCAGAAAGCGAA PPARG-F Peroxisome proliferator-activated receptor gamma NM_015869.4 ACAGATCCAGTGGTTGCAGA PPARG-R Peroxisome proliferator-activated receptor gamma NM_015869.4 TCCACTTTGATTGCACTTTGGT CEBPA-F CCAAT/enhancer binding protein (C/EBP), alpha NM_001287424.1 CCCAGAGGGACCGGAGTTAT CEBPA-R CCAAT/enhancer binding protein (C/EBP), alpha NM_001287424.1 AGACGCGCACATTCACATTG ACSL1-F Acyl-CoA synthetase long-chain family member 1 NM_001286708.1 CTTCTGGTACGCCACGAGAC ACSL1-R Acyl-CoA synthetase long-chain family member 1 NM_001286708.1 GTCGCTGTCAAGTAGTGCG CD36-F CD36 molecule (thrombospondin receptor) NM_000072.3 CCTGGCTGTGTTTGGAGGTAT CD36-R CD36 molecule (thrombospondin receptor) NM_000072.3 CTTCGAGGACAACTTGCTTTT FABP4-F Fatty acid binding protein 4, adipocyte NM_001442.2 ATGGGGGTGTCCTGGTACAT FABP4-R Fatty acid binding protein 4, adipocyte NM_001442.2 TCGTGGAAGTGACGCCTTTC PLIN1-F Perilipin 1, transcript variant 1 NM_002666 GACAAGGAAGAGTCAGCCCC PLIN1-R Perilipin 1, transcript variant 1 NM_002666 GAGAGGGTGTTGGTCAGAGC ADIPOQ-F Adiponectin, C1Q and collagen domain containing NM_001177800 AAGGAGATCCAGGTCTTATTGGT ADIPOQ-R Adiponectin, C1Q and collagen domain containing NM_001177800 GTTCTCCTTTCCTGCCTTGGA ANGPTL4 -F Angiopoietin-like 4, transcript variant 1 NM_139314.2 TCCACCGACCTCCCGTTAG ANGPTL4-R Angiopoietin-like 4, transcript variant 1 NM_139314.2 GGCCACCTTGTGGAAGAGTT

Table S2. Mouse SYBR green RT-qPCR primers

Name Full Name Accession Number 5' – 3' Sequence

Tbp-F TATA box binding protein NM_013684.3 GCACAGGAGCCAAGAGTGAA

Tbp-R TATA box binding protein NM_013684.3 TAGCTGGGAAGCCCAACTTC

Cpt1a-F Carnitine palmitoyltransferase 1a, liver NM_013495.2 GGGCCATCTGTGGGAGTATG Cpt1a-R Carnitine palmitoyltransferase 1a, liver NM_013495.2 ACTGTAGCCTGGTGGGTTTG Ppara-F Peroxisome proliferator activated receptor alpha NM_011144.6 CAACAACCCGCCTTTTGTCA Ppara-R Peroxisome proliferator activated receptor alpha NM_011144.6 TCTTTGTCTTCGACGCCGTT Scd1-F Stearoyl-Coenzyme A desaturase 1 NM_009127.4 AAAGCCGAGAAGCTGGTGAT Scd1-R Stearoyl-Coenzyme A desaturase 1 NM_009127.4 TACAAAAGTCTCGCCCCAGC Srebf1-F Sterol regulatory element binding transcription factor 1 NM_011480.3 GCACACAAAAGCAAATCACTG

Referanser

Last ned nå ( PDF - 7 sider - 788.37 KB )

RELATERTE DOKUMENTER

A mechanistic study of functional polymorphisms in the MDM2 gene

These putative transcription factor binding sites for G/G may explain the increased risk of cancer with an increased MDM2 transcriptional activity which again leads to

Fatty acid induced changes in gene expression in cultured L6 rat muscle cells : An in vitro model on high dietary fat-induced insulin resistance in red gastrocnemius rat muscle in vivo

The results from the comparisons above together with the results showing that genes involved in cholesterol biosynthesis, fatty acid synthesis and sterol regulation are

Mechanism of SUMO repression of the transcription factor c-Myb – the role of SUMO acetylation

The proteins interact with c-Myb and enhance its transcriptional activity by recruiting the transcription factor to Myb binding sites of target genes (Pattabiraman, McGirr et

Prospects for viruses infecting eukaryotic microalgae in biotechnology

(1) Viral genetic regulatory elements (e.g. promoters, terminators, ribosome binding sites, transcription enhancers, etc.) can be predicted and isolated from the viral genomes,

Regulatory architecture of gene expression variation in the threespine stickleback Gasterosteus aculeatus

Since transcription is typically initiated by a complex of genes rather than a single transcription factor, we examined functional relationships among the identified upstream

1 2 3 2 3

sikkerhetsnivået på jernbanenettet. En av intervjupersonene sa det på denne måten: «Piloten har på sett og vis vært et samarbeidsprosjekt mellom JBV og Statens jernbanetilsyn for

1 5

Spania hadde i ai samme jevne veksten i fothket av n m k laks som de andre europeiske importlandene, til m8nedsskif- tet aptillmai. Vi har ikke hatt noen star-

1 5

I Moskenes kommune er det en konsesjon for oppdrett av laks og ørret,