Synthesis and biological activity of N-isopimaryl-N'-aromatic heterocyclic thiourea derivatives
As one of the most important renewable resources,rosin and its derivatives have good biological activities due to its tricyclic structure.Heterocyclic acylthiourea compounds have a special molecular configuration that can be modified with a variety of structures and spliced with isopimaric acid,which has good biological activity to obtain compounds with different biological activities.To develop isopimaric acid derivatives with high bioactivity,isopimaryl isothiocyanate was synthesized by first chlorination then reacted with potassiumthiocyanate using isopimaric acid as a raw material.Then,a series of novel N-isopimaryl-N'-aromatic heterocyclic thiourea derivatives(4a-4j)such as N-isopimaryl-N'-(3-pyridyl)thiourea(4a),N-isopimaryl-N'-(5-bromo-2-pyridyl)thiourea(4b),N-isopimaryl-N'-(2-chloro-5-pyridyl)thiourea(4c),N-isopimaryl-N'-(2-pyridyl)thiourea(4d),N-isopimaryl-N'-(2-thiazolyl)thi-ourea(4e),N-isopimaryl-N'-(5-quinolyl)thiourea(4f),N-isopimaryl-N'-(3-isoquinolyl)thiourea(4g),N-isopimaryl-N'-(pyrrolo[2,1-f][1,2,4]triazinyl)thiourea(4h),N-isopimaryl-N'-(4,6-dimethoxy-2-pyrimidinyl)thiourea(4i),N-isopimaryl-N'-(5,8-dimethoxy-[1,2,4]triazolo[1,5-c]pyrimidinyl)thiourea(4j)were synthe-sized through isopimaryl isothiocyanate reacts with different heterocyclic substituted amines.The structures of N-isopi-maryl-N'-aromatic heterocyclic thiourea derivatives were characterized by the infrared spectrometry(FT-IR),hydrogen nuclear magnetic resonance spectroscopy(1 H NMR),carbon nuclear magnetic resonance spectroscopy(13C NMR)and mass spectrometry(MS).The minimum inhibitory concentrations of the compounds against five bacteria or fungus were determined and in vitro antitumor activities of the compounds were investigated.The results showed that most N-isopimaryl-N'-aromatic heterocyclic thiourea derivatives exhibited a certain fungicidal activity on Staphylococcus aureus,especially compounds 4b,4c,4d,4e and 4f showed the best antibacterial activity.Com-pounds 4b,4c,4d,4e and 4f showed a minimum inhibitory mass concentration of 0.98 μg/mL against S.aureus,which is better than that of the positive control benzylpenicillin sodium.The minimum inhibitory mass concentration of compounds 4h against SS.aureus was 15.60 μg/mL.The minimum inhibitory concentration of compounds 4i and 4j against S.aureus were both 31.30 µg/mL.Most N-isopimaryl-N'-aromatic heterocyclic thiourea derivatives showed poor bacteriostatic activity against Sphaeropsis sapinea(Fr.)Dyko &B.Sutton and Heterobasidion|ecrustosum To-kuda T.Hatt.&Y.C.Dai.When the concentration of the compounds was 100 μmol/L,some of the compounds had good antitumor activity.The inhibition rate of compounds 4f and 4g against hepatocarcinoma cells(Hep G2)were 68.59％and 82.30％,respectively.The inhibition rate of compounds 4g against cervical cancer cells(Hela),breast cancer cells(MDA-MB-231),and prostate cancer cells(PC-3)were 80.74％,71.21％and 62.14％,respectively.All the N-isopimaryl-N'-aromatic heterocyclic thiourea derivatives showed low antitumor activity at concertration 10μmol/L.
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