3.5.4.4: adenosine deaminase

(2S,3R)-3-(6-amino-9H-purin-9-yl)-5-[3-(trifluoromethyl)phenyl]pentan-2-ol

comopound shows suitable balance of potency, microsomal stability and demonstrates better pharmacokinetic properties as compared to (+)-erythro-9-(2-hydroxy-3-nonyl)adenine

752963

(2S,3R)-3-(6-amino-9H-purin-9-yl)-5-[4-(trifluoromethyl)phenyl]pentan-2-ol

comopound shows suitable balance of potency, microsomal stability and demonstrates better pharmacokinetic properties as compared to (+)-erythro-9-(2-hydroxy-3-nonyl)adenine

752963

(2S,3R)-3-(6-amino-9H-purin-9-yl)nonan-2-ol

(S)-(-)-epoxydecane

1,6-Dihydro-6-(hydroxymethyl)purine riboside

209615

1-(4-benzylphenyl)-3-[4-[(4-oxo-4,5-dihydro-2H-pyrazolo[3,4-d]pyrimidin-2-yl)methyl]phenyl]urea

1-(4-fluorophenyl)-3-[4-[(4-oxo-4,5-dihydro-2H-pyrazolo[3,4-d]pyrimidin-2-yl)methyl]phenyl]urea

1-(4-methoxyphenyl)-3-[4-[(4-oxo-4,5-dihydro-2H-pyrazolo[3,4-d]pyrimidin-2-yl)methyl]phenyl]urea

1-(hydroxymethyl)nonyl methanesulfonate

1-(tert-butyldimethylsilanyloxy)-decan-2-ol

1-(tert-butyldimethylsilanyloxymethyl)nonyl methanesulfonate

1-alkyl-3-amino-4-pyrazolecarbonitriles

1-alkyl-4-aminopyrazolo[3,4d]pyrimidines

1-benzyl-3-[4-[(4-oxo-4,5-dihydro-2H-pyrazolo[3,4-d]pyrimidin-2-yl)methyl]phenyl]urea

1-deaza-erythro-9-(2-hydroxy-3-nonyl)adenine

1-deazaadenosine

1-methyl adenosine

1-[(1R)-1-(hydroxymethyl)-3-(6-[[(1-methyl-1H-benzimidazol-2-yl)acetyl]amino]-1H-indol-1-yl)propyl]-1H-imidazole-4-carboxamide

1-[(1R)-1-(hydroxymethyl)-3-naphthalen-1-ylpropyl]-1H-imidazole-4-carboxamide

1-[(1R)-1-(hydroxymethyl)-3-phenylpropyl]-1H-imidazole-4-carboxamide

1-[(1R)-2-hydroxy-1-phenylethyl]-1H-imidazole-4-carboxamide

1-[(1R)-3-[6-(acetylamino)-1H-indol-1-yl]-1-(hydroxymethyl)propyl]-1H-imidazole-4-carboxamide

1-[(1R)-3-[6-(hexanoylamino)-1H-indol-1-yl]-1-(hydroxymethyl)propyl]-1H-imidazole-4-carboxamide

1-[(1R,2S)-2-hydroxy-1-(2-naphthalen-1-ylethyl)propyl]-1H-imidazole-4-carboxamide

1-[(2S,3R)-2,3-dihydroxycyclopentyl]-5-(1,3-thiazol-5-yl)pyrimidine-2,4(1H,3H)-dione

28% inhibition at 0.1 mM

1-[(2S,3R)-2,3-dihydroxycyclopentyl]-5-(furan-2-yl)pyrimidine-2,4(1H,3H)-dione

35% inhibition at 0.1 mM

1-[(2S,3R)-2,3-dihydroxycyclopentyl]-5-(thiophen-2-yl)pyrimidine-2,4(1H,3H)-dione

36% inhibition at 0.1 mM

1-[(3R,4S)-4-hydroxy-1-[3-(trifluoromethyl)phenyl]pentan-3-yl]-1H-imidazole-4-carboxamide

comopound shows suitable balance of potency, microsomal stability and demonstrates better pharmacokinetic properties as compared to (+)-erythro-9-(2-hydroxy-3-nonyl)adenine

752963

1-[(4R,5S)-4,5-dihydroxycyclopent-2-en-1-yl]-5-(1,3-thiazol-5-yl)pyrimidine-2,4(1H,3H)-dione

49% inhibition at 0.1 mM

1-[(4R,5S)-4,5-dihydroxycyclopent-2-en-1-yl]-5-(furan-2-yl)pyrimidine-2,4(1H,3H)-dione

55% inhibition at 0.1 mM

1-[(4R,5S)-4,5-dihydroxycyclopent-2-en-1-yl]-5-(thiophen-2-yl)pyrimidine-2,4(1H,3H)-dione

48% inhibition at 0.1 mM

1-[(R)-1-hydroxy-4-(1-methyl-5-(3-phenylpropoxy)indol-3-yl)-2-butyl]imidazole-4-carboxamide

1-[(R)-1-hydroxy-4-(5-(3-phenylpropoxy)indol-1-yl)-2-butyl]imidazole-4-carboxamide

1-[(R)-1-hydroxy-4-(6-(3-(1-methylbenzimidazol-2-yl)propionylamino)indol-1-yl)-2-butyl]imidazole-4-carboxamide

1-[(R)-1-hydroxy-4-(6-(3-(3-pyridyl)propionylamino)indol-1-yl)-2-butyl]imidazole-4-carboxamide

1-[(R)-1-hydroxy-4-(6-(3-(4-methoxyphenyl)propionylamino)indol-1-yl)-1-hydroxy-2-butyl]imidazole-4-carboxamide

1-[(R)-1-hydroxy-4-(6-(3-(4-methylphenyl)propionylamino)indol-1-yl)-2-butyl]imidazole-4-carboxamide

1-[(R)-1-hydroxy-4-(6-(3-phenylpropionylamino)indol-1-yl)-2-butyl]imidazole-4-carboxamide

1-[(R)-1-hydroxy-4-(6-(3-phenylpropoxy)indol-1-yl)-2-butyl]imidazole-4-carboxamide

1-[(R)-1-hydroxy-4-(6-(4-(4-methylphenyl)butyrylamino)indol-1-yl)-2-butyl]imidazole-4-carboxamide

1-[(R)-1-hydroxy-4-(6-(4-phenylbutoxy)indol-1-yl)-2-butyl]imidazole-4-carboxamide

1-[(R)-1-hydroxy-4-(6-(4-phenylbutyrylamino)indol-1-yl)-2-butyl]imidazole-4-carboxamide

1-[(R)-1-hydroxy-4-(6-(5-phenylvalerylamino)indol-1-yl)-2-butyl]imidazole-4-carboxamide

1-[(R)-1-hydroxy-4-(6-(6-phenylhexanoylamino)indol-1-yl)-2-butyl]imidazole-4-carboxamide

1-[(R)-4-(5-(3-(4-chlorophenyl)propoxyl)-1-methylindol-3-yl)-1-hydroxy-2-butyl]imidazole-4-carboxamide

1-[(R)-4-(5-hexyloxy-1-methylindol-3-yl)-1-hydroxy-2-butyl]imidazole-4-carboxamide

1-[(R)-4-(5-hexyloxyindol-1-yl)-1-hydroxy-2-butyl]imidazole-4-carboxamide

1-[(R)-4-(6-(3-(4-chlorophenyl)propoxy)indol-1-yl)-1-hydroxy-2-butyl]imidazole-4-carboxamide

1-[(R)-4-(6-(3-benzylureido)indol-1-yl)-1-hydroxy-2-butyl]imidazole-4-carboxamide

1-[(R)-4-(6-acetylaminoindol-1-yl)-1-hydroxy-2-butyl]imidazole-4-carboxamide

1-[(R)-4-(6-butoxyindol-1-yl)-1-hydroxy-2-butyl]imidazole-4-carboxamide

1-[(R)-4-(6-hexanoylaminoindol-1-yl)-1-hydroxy-2-butyl]imidazole-4-carboxamide

1-[(R)-4-(6-hexyloxyindol-1-yl)-1-hydroxy-2-butyl]imidazole-4-carboxamide

1-[4-(dimethylamino)phenyl]-3-[4-[(4-oxo-4,5-dihydro-2H-pyrazolo[3,4-d]pyrimidin-2-yl)methyl]phenyl]urea

1-[4-[(4-oxo-4,5-dihydro-2H-pyrazolo[3,4-d]pyrimidin-2-yl)methyl]phenyl]-3-(4-phenoxyphenyl)urea

1-[4-[(4-oxo-4,5-dihydro-2H-pyrazolo[3,4-d]pyrimidin-2-yl)methyl]phenyl]-3-phenylurea

1-[4-[(4-oxo-4,5-dihydro-2H-pyrazolo[3,4-d]pyrimidin-2-yl)methyl]phenyl]-3-[4-(trifluoromethyl)phenyl]urea

2',3'-o-isopropyliden adenosine

209637

2'-deoxy-4-amino-1-(beta-D-ribofuranosyl)-3H-imidazo[4,5-d]pyridazin-7-(6H)-one

2'-deoxy-7-amino-1-(beta-D-ribofuranosyl)-1H-imidazo[4,5-d]pyridazin-4-(5H)-one

2'-deoxycoformycin

2'-deoxyformycin

50% inhibition of isozyme ADA2 at 0.09 mM

667870

2'-deoxyinosine

209606

2,2,2-trifluoro-N-[7-chloro-5-methyl-3-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-3H-imidazo[4,5-b]pyridin-6-yl]-acetamide

20% inhibition at 0.4 mM

2,2,2-trifluoro-N-[7-chloro-5-methyl-3-(beta-D-ribofuranosyl)-3H-imidazo[4,5-b]pyridin-6-yl]acetamide

23% inhibition at 0.4 mM

2,6-diaminopurine

2,6-diaminopurine sulfate

2-alkyl-4-aminopyrazolo[3,4d]pyrimidines

2-Amino-4-hydroxypteridine

2-Aminopurine

2-Deoxycoformycin

2-mercaptoethanol

Aspergillus terricola

209631

3-amino-1-(2-hydroxy-3-nonyl)4-pyrazolecarbonitrile

3-amino-1-(2-keto-3-nonyl)4-pyrazolecarbonitrile

3-amino-1-beta-hydroxyalkyl-4-pyrazolecarbonitriles

3-deaza-erythro-9-(2-hydroxy-3-nonyl)adenine

3-deazaadenosine

4-acetylamino-2-decylpyrazolo[3,4d]pyrimidine

4-amino-1-(2-hydroxy-3-nonyl)pyrazolo[3,4d]pyrimidine

4-amino-1-(beta-D-ribofuranosyl)-3H-imidazo[4,5-d]pyridazin-7-(6H)-one

4-amino-1-(beta-hydroxyethyl)pyrazolo[3,4d]pyrimidine

4-amino-1-(beta-hydroxyoctyl)pyrazolo[3,4d]pyrimidine

4-amino-2-(2-hydroxy-1-decyl)pyrazole[3,4-d]pyrimidine

i.e. APP

688598

4-amino-2-decyl-6-phenylpyrazolo[3,4d]pyrimidine

4-amino-5-imidazole carboxamide-HCl

4-amino-5-imidazole carboxyamide ribonucleoside

4-aminopyridine

competitive inhibition

4-aminopyrimidine

competitive inhibition

4-fluoro-N-[4-[(4-oxo-4,5-dihydro-2H-pyrazolo[3,4-d]pyrimidin-2-yl)methyl]phenyl]benzamide

4-hydroxypyridine

competitive inhibition

4-methoxy-N-[4-[(4-oxo-4,5-dihydro-2H-pyrazolo[3,4-d]pyrimidin-2-yl)methyl]phenyl]benzamide

5'-methylthio-2'-deoxycoformycin

Plasmodium falciparum

687290

5'-methylthiocoformycin

7 entries

5-(beta-D-ribofuranosyl)-1H,5H-imidazo[4,5-b]pyrazolo[3,4-e]pyridine

25% inhibition at 0.4 mM

5-carbamimidoyl-1-(beta-D-ribofuranosyl)-1H-imidazole-4-carbohydrazide

5-methyl-3-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-3H-imidazo[4,5-b]pyridin-6-amine

19% inhibition at 0.4 mM

5-methyl-3-(beta-D-ribofuranosyl)-3H-imidazo[4,5-b]pyridin-6-amine

6% inhibition at 0.4 mM

5-methyl-6-nitro-3-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-3H-imidazo[4,5-b]pyridine

31% inhibition at 0.4 mM

5-methyl-6-nitro-3-(beta-D-ribofuranosyl)-3H-imidazo[4,5-b]pyridine

25% inhibition at 0.4 mM

6-Chloropurine

6-fluoro-D,L-tryptophan

adenosine analogue, induces conformational changes inhibiting the enzyme, structural mechanism, overview

669846

6-methylamino riboside

6-Methylmercaptopurine riboside

7,8-dihydro-1-p-methoxybenzyl-6H-6,7-dimethyl-8-propoxyimidazo[4,5-e][1,2,4]-triazepine

7,8-dihydro-1-p-methoxybenzyl-8-(2-methoxyethoxy)-6H-6,7-dimethylimidazo[4,5-e][1,2,4]triazepine

7,8-dihydro-1-p-methoxybenzyl-8-(3-methylbenzyloxy)-6H-6,7-dimethylimidazo[4,5-e][1,2,4]triazepine

7,8-dihydro-1-p-methoxybenzyl-8-(4-methoxybenzyloxy)-6H-6,7-dimethylimidazo[4,5-e][1,2,4]triazepine

7,8-dihydro-8-ethoxy-1-p-methoxybenzyl-6H-6,7-dimethylimidazo[4,5-e][1,2,4]triazepine

7,8-dihydro-8-isopropoxy-1-p-methoxybenzyl-6H-6,7-dimethylimidazo[4,5-e][1,2,4]triazepine

7,8-dihydro-8-methoxy-1-p-methoxybenzyl-6H-6,7-dimethylimidazo[4,5-e][1,2,4]triazepine

7-(beta-D-ribofuranosyl)-1H,7H-imidazo[4,5-b]pyrazolo[3,4-e]pyridine

7% inhibition at 0.4 mM

7-amino-1-(beta-D-ribofuranosyl)-1H-imidazo[4,5-d]pyridazin-4-(5H)-one

7-chloro-5-methyl-3-(beta-D-ribofuranosyl)-3H-imidazo[4,5-b]pyridin-6-amine

15% inhibition at 0.4 mM

8-Bromoadenosine

Nocardioides sp.

209630

8-butoxy-7,8-dihydro-1-p-methoxybenzyl-6H-6,7-dimethylimidazo[4,5-e][1,2,4]triazepine

9-(p-aminobenzyl)adenine

209608

acetaminophen

competitive at 27°C, uncompetitive at 37°C

Acetylsalicylic acid

adenine

adenosine analogs

adenosine analogues

induce conformational changes inhibiting the enzyme, structural mechanism, overview

669846

adenosine monosulfate

Ag+

Ag2+

aminoxyacetic acid

Micrococcus sodonensis

209609

AMP

Candida albicans

209636

aspirin

significantly decreases adenosine deaminase activity, the half-life of adenosine will be lengthened as a consequence of decreased adenosine deaminase activity

695585

ATP

Azotobacter vinelandii

209623

aza adenosine analogues

209633

Ba2+

Fasciola gigantica

44% inhibition at 5 mM

686612

basic histone proteins

Xenopus laevis

209629

Ca2+

caffeic acid phenethyl ester

reduces the enzyme activity in vivo, suppresses the induction of the enzyme by cisplatin in vivo

Caffeine

Cd2+

Co2+

coformycin

cordycepin

corticosterone

Cu2+

D-coformycin

deaza adenosine analogues

Deoxycoformycin

DEPC

diclofenac

competitive at 27°C, uncompetitive at 37°C

688029

diethyl dicarbonate

654788

dodecyltrimethylammonium bromide

at low concentrations (approximately 0.1 mM), enzyme activity decreases, it increases at a slightly higher concentration (about 0.2 mM), and finally decreases again (about 0.3 mM), CD spectra of adenosine deaminase and DTAB, determination of helix content, MD calculations

EDTA

epigallocatechin gallate

most abundant and biologically active ?avonoid present in green tea, strong competitive inhibitory activity

756517

erythro-9-(2-hydroxy-3-nonyl)-3-deazaadenine

654788

erythro-9-(2-hydroxy-3-nonyl)-adenine

erythro-9-(2-hydroxy-3-nonyl)-adenine hydrochloride

erythro-9-(2-hydroxy-3-nonyl)adenine

15 entries

erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride

ethanol

CD spectra of adenosine deaminase and EtOH, determination of helix content, MD calculations

Fe2+

Klebsiella sp.

209628

folic acid

209606

FR234938

i.e. 1-((1R,2S)-2-hydroxy-1-(2-(1-naphthyl)ethyl)propyl)1H-imidazole-4-carboxamine, a non-nucleoside inhibitor, the inhibition is blocked by an A2a adenosine receptor antagonist

guanosine

heparin

Hg2+

HgCl2

inhibition of ADA activity is observed in the soluble fraction at 0.005-0.25 mM HgCl2 (84.6-92.6% respectively), whereas inhibition occurs at 0.005-0.25 mM in membrane fractions (20.9-26% respectively). The inhibition is partially or fully abolished by 0.5 mM dithiothreitol or EDTA

713127

hypoxanthine

209606

IgG

anti adenosine deaminase

209625

indole-3-acetic acid

the plant hormone decreases enzyme activity in hearts, but not in kidney and muscle

667361

Inosine

4 entries

iodoacetamide

Micrococcus sodonensis

iodoacetic acid

Iodopurine

isosorbide mononitrate

significantly decreases adenosine deaminase activity, the half-life of adenosine will be lengthened as a consequence of decreased adenosine deaminase activity

K+

kinetin

the plant hormone decreases enzyme activity in hearts, but not in kidney and muscle

L-cysteine

lysozyme

methanol

MD calculations, discussion of effects

methylmercury

concentration 0.1, 1.0, 20 M, inhibits adenosine deaminase activity in 7- and 60-day-old rats in a concentration-dependent manner, glutathione (50 microM) and dithiothreitol (50 microM) prevent the reduction of adenosine deaminase activity both in cerebral cortex and hippocampus, garlic alcoholic extract (100 microg/ml) abolishes the reduction of adenosine deaminase

695973

metoprolol

significantly decreases adenosine deaminase activity, the half-life of adenosine will be lengthened as a consequence of decreased adenosine deaminase activity

Mg2+

Mn2+

N-ethylmaleimide

N-[4-[(4-oxo-4,5-dihydro-2H-pyrazolo[3,4-d]pyrimidin-2-yl)methyl]phenyl]-2-phenylacetamide

N-[4-[(4-oxo-4,5-dihydro-2H-pyrazolo[3,4-d]pyrimidin-2-yl)methyl]phenyl]-4-(trifluoromethyl)benzamide

N-[4-[(4-oxo-4,5-dihydro-2H-pyrazolo[3,4-d]pyrimidin-2-yl)methyl]phenyl]benzamide

N6-methyladenosine

Na+

Na2SO4

CD spectra of adenosine deaminase and Na2SO4, determination of helix content, MD calculations, discussion of effects

NaCl

MD calculations, discussion of effects

nebularine

i.e. 9-beta-D-ribofuranosylpurine, competitive inhibitor

NH4+

Ni2+

o-phenanthroline

p-chloromercuribenzoate

7 entries

p-chloromercuryphenylsulfonate

209605

p-hydroxymercuribenzoic acid

Candida albicans

209636

Pb2+

Micrococcus sodonensis

Pentachlorophenol

pentostatin

phenylhydrazine

competitive inhibition

progesterone

progesterone decreases adenosine deaminase levels, adenosine deaminase levels show regional specificity with differences among the cerebral hemispheres, cerebellum, and brainstems structures

698351

purine

competitive inhibition

purine riboside

6 entries

reduced glutathione

Aspergillus terricola

209631

simvastatin

inhibits ADA1 activity by 46.7%; significantly decreases adenosine deaminase activity, the half-life of adenosine will be lengthened as a consequence of decreased ADA activity

695585

Sodium dodecyl sulfate

at low concentrations (approximately 0.1 mM) enzyme activity decreases, it increases at a slightly higher concentration (about 0.4 mM), and finally decreases again (about 0.55 mM), CD spectra of adenosine deaminase and SDS, determination of helix content, MD calculations

Sodium selenate