文献类型：期刊文献

中文题名：N-异海松酰基-N′-芳杂环基硫脲类衍生物的合成及生物活性

英文题名：Synthesis and biological activity of N-isopimaryl-N′-aromatic heterocyclic thiourea derivatives

作者：卢言菊[1,2] 陈玉湘[2,3] 王婧[2,3] 徐士超[2,3] 黄申林[1,2]

第一作者：卢言菊

机构：[1]南京林业大学化学工程学院,南京210037;[2]南京林业大学林业资源高效加工利用协同创新中心,南京210037;[3]中国林业科学研究院林产化学工业研究所,南京210042

年份：2024

卷号：9

期号：3

起止页码：69-76

中文期刊名：林业工程学报

外文期刊名：Journal of Forestry Engineering

收录：CSTPCD;;Scopus;北大核心:【北大核心2023】；CSCD:【CSCD_E2023_2024】；

基金：国家自然科学基金(32271818);中央级公益性科研院所基本科研业务费专项资金(CAFYBB2022MA003)。

语种：中文

中文关键词：异海松酸;N′-芳杂环硫脲类化合物;合成;抑菌活性;抗肿瘤活性

外文关键词：isopimaric acid;N′-aromatic heterocyclic thiourea derivatives;synthesis;antibacterial activity;antitumor activity

分类号：TQ351.0

摘要：为得到潜在的新型抑菌剂和抗肿瘤药物,笔者以异海松酸为原料,先与草酰氯反应制备得到异海松酰氯,后与硫氰化钾反应生成异海松酰基异硫氰酸酯,在此基础上与不同杂环取代胺反应,设计并合成了10个新型N-异海松酰基-N′-芳杂环基硫脲类衍生物4a~4j,采用傅里叶红外光谱(FT-IR)、氢核磁共振(1H NMR)、碳核磁共振(13C NMR)和质谱(MS)等手段确定了目标化合物的结构,研究了N-异海松酰基-N′-芳杂环基硫脲类衍生物的抑菌及抗肿瘤活性。研究结果表明,大部分N-异海松酰基-N′-芳杂环基硫脲类衍生物对金黄色葡萄球菌都具有良好的抑菌活性,其中化合物4b、4c、4d、4e和4f对金黄色葡萄球菌的最低抑菌质量浓度达到0.98μg/mL,优于对照物青霉素钠,其中化合物4h的最低抑菌质量浓度也达到15.60μg/mL;化合物4i和4j的最低抑菌质量浓度为31.30μg/mL,大部分衍生物对樟子松枯梢病菌和无壳异担子菌无明显的抑菌活性。在浓度为100μmol/L时,部分N-异海松酰基-N′-芳杂环基硫脲类衍生物具有较好的抗肿瘤活性,化合物4f和4g对肝癌细胞的体外抑制率分别为68.59%和82.30%,化合物4g对宫颈癌细胞、前列腺癌细胞和乳腺癌细胞的体外抑制率分别为80.74%、71.21%和62.14%。
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)thiourea(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 synthesized through isopimaryl isothiocyanate reacts with different heterocyclic substituted amines.The structures of N-isopimaryl-N′-aromatic heterocyclic thiourea derivatives were characterized by the infrared spectrometry(FT-IR),hydrogen nuclear magnetic resonance spectroscopy(1H 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.Compounds 4b,4c,4d,4e and 4f showed a minimum inhibitory mass concentration of 0.98μg/mL against S.aureus,which is better than that of the positive control benzylpenicillin sodium.The minimum inhibitory mass concentration of compounds 4h against S.aureus was 15.60μg/mL.The minimum inhibitory concentration of compounds 4i and 4j against S.aureus were both 31.30μg/mL.Most N-isopimaryl-N′-aromatic heterocyclic thiourea derivatives showed poor bacteriostatic activity against Sphaeropsis sapinea(Fr.)Dyko&B.Sutton and Heterobasidion│ecrustosum Tokuda T.Hatt.&Y.C.Dai.When the concentration of the compounds was 100μmol/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.