Synthesis of 3-((1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)thio)propanoic acid (2)

Synthesis of methyl 3-((1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)thio)propanoate (3)

Synthesis of 3-((1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)thio)propano hydrazide (4)

General procedure for syntheses of hydrazide-hydrazones of 3-((1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)thio)propanoic acid (6a-p)

Synthesis of N‘-benzylidene-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6a)

Synthesis of N‘-(4-nitrobenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6b)

Synthesis of N‘-(2,6-dichlorobenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6c)

Synthesis of N‘-(3-chlorobenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6d)

Synthesis of N‘-(4-bromobenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6e)

Synthesis of N‘-(4-(trifluoromethyl)benzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6f)

Synthesis of N‘-(3,4-dimethoxybenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6g)

Synthesis of N‘-(3,4,5-trimethoxybenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6h)

Synthesis of N‘-(4-hydroxy-3,5-dimethoxybenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6i)

Synthesis of N‘-(4-hydroxy-3-methoxybenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6j)

Synthesis of N‘-(2,3-dimethoxybenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6k)

Synthesis of N‘-(2-hydroxybenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6l)

Synthesis of 3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)-N‘-(2,4,6-trimethylbenzylidene)propanehydrazide (6m)

Synthesis of N‘-(2-hydroxy-3-methoxybenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6n)

Synthesis of N‘-(3-nitrobenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6o)

Synthesis of N‘-(4-hydroxy-3-methoxy-5-nitrobenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6p)

Animals

Isolation and incubation of microsomes

Measurement of malondialdehyde (MDA) in isolated rat microsomes

Statistical analysis

Prediction of the site of metabolism (SOM)

Hepatotoxicity evaluation– effects on isolated rat liver microsomes