异长叶烷基噻唑类化合物的合成及其生物活性

doi:10.3969/j.issn.1000-2006.2017.01.023

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南京林业大学学报（自然科学版） ›› 2017, Vol. 60 ›› Issue (01): 149-155.doi: 10.3969/j.issn.1000-2006.2017.01.023

异长叶烷基噻唑类化合物的合成及其生物活性

芮坚¹,蔡涛¹,杨金来¹,杨益琴²,徐徐¹,王石发^1*

1.南京林业大学化学工程学院, 江苏省林业资源高效加工利用协同创新中心,江苏省生物质绿色燃料与化学品重点实验室,江苏南京 210037;
2.南京林业大学轻工科学与工程学院,江苏南京 210037

出版日期:2017-02-18 发布日期:2017-02-18
基金资助:
基金项目:江苏省生物质能源与材料重点实验室开放基金项目(JSBEM2014010); 教育部高等学校博士学科点科研基金项目(20123204120010)
第一作者:芮坚(1044603872@qq.com)。*通信作者:王石发(wsfyyq@njfu.com),教授。

Synthesis and bioactivities evaluation of isolongifolanyl thiazole derivatives

RUI Jian¹, CAI Tao¹, YANG Jinlai¹, YANG Yiqin², XU Xu¹, WANG Shifa^1*

1.College of Chemical Engineering, Nanjing Forestry University, Jiangsu Co-Innovation Center of Efficient Process and Utilization of Forest Resources, Jiangsu Key Laboratory Biomass Green Fuels and Chemicals, Nanjing 210037, China;
2. College of Light Industry Science and Engineering, Nanjing Forestry University, Nanjing 210037, China

Online:2017-02-18 Published:2017-02-18

摘要/Abstract

摘要： 【目的】将噻唑环构建至异长叶烷酮分子中,得到具有新型生物活性化合物,拓展松节油的应用领域,提高松节油的利用价值。【方法】异长叶烷酮与氨基硫脲缩合,生成异长叶烷酮缩氨基硫脲; 异长叶烷酮缩氨基硫脲再与α-溴代苯乙酮衍生物发生环化反应,得到11种异长叶烷基噻唑类化合物2a—2k。采用FT-IR、¹H NMR、¹³C NMR、HPLC-MS等手段,对合成产物的结构进行了表征。采用最低抑制浓度(MIC)法和MTT法分别研究了异长叶烷基噻唑类化合物的抑菌活性和抗肿瘤活性。【结果】化合物4-(4-氯苯基)-2-(2-(1,1,5,5)-四甲基四氢-1H-2,4α-桥亚甲基萘-8(2H,5H,8αH)-亚基)肼基)噻唑(2b)和4-(2-萘基)-2-(2-(1,1,5,5)-四甲基四氢-1H-2,4α-桥亚甲基萘-8(2H,5H,8αH)-亚基)肼基)噻唑(2j)对枯草芽孢杆菌与荧光假单胞菌抑制效果较好,其最低抑制浓度(MIC)为7.5 μg/mL,化合物2b对真菌(白色念球菌与热带假丝酵母菌)的抑制效果优于其他化合物,其MIC值均为15.6 μg/mL; 异长叶烷酮缩氨基硫脲对人体肝癌细胞HepG2 的半抑制浓度(IC₅₀)为(34.5±0.8)μg/mL,表明其对HepG2具有较好的抗癌活性。【结论】异长叶烷酮缩氨基硫脲可作为潜在的抗肿瘤药物。

Abstract: 【Objective】This research is to construct the thiazole ring into the molecular skeleton of isolongifolanone for obtaining some new types of compounds with biological activity, developing the new application field and improving the utilization value of gum turpentine.【Method】Eleven novel isolongifolanyl thiazole derivatives(2a-2k)were synthesized by condensation and cyclization from isolongifolanone. Isolongifolanone was condensed with thiosemicarbazide to get the intermediate isolongifolanyl thiosemicarbazones, which was further cyclized with SymbolaA@-bromoacetophenone derivatives to obtain the compound 2a-2k. The structures of compound 2a-2k were characterized with FT-IR,¹H NMR, ¹³C NMR, and HPLC-MS. The antimicrobial and antitumor activities of 2a-2k were investigated with minimum inhibitory concentrations assay(MIC)and MTT assay, respectively.【Result】The antibacterial activities of 4-(4-chlorophenyl)-2-(2-(1,1,5,5-tetramethyltetrahydro-1H-2,4SymbolaA@-methanonaphthalen-8-(2H,5H,8αH)-ylidene)hydrazinyl)thiazole(2b)and 4-(naphthalen-2-yl)-2-(2-(1,1,5,5-tetramethyl-tetrahydro-1H-2,4SymbolaA@-methanonaphthalen-8(2H,5H,8αH)-ylidene)hydrazinyl)thiazole(2j)were better than that of others against Bacillus subtilis and Pseudomonas fluorescens, and their MIC were 7.5 μg/mL. The antibacterial activity of compound 2b was better than that of others against fungus, and its MIC values against Candida albicans and Candida tropicalis was 15.6 μg/mL. It was also found that the antitumor activities of isolongifolanyl thiosemicarbazide against HepG2 was the best than that of its cyclized derivatives, and its IC₅₀ was(34.5±0.8)μg/mL which was at the same level with that of the standard sample etoposide.【Conclusion】Isolongifolanyl thiosemicarbazide has the potential to be a new drug against HepG2 and deserves further research.

中图分类号:

TQ251

芮坚,蔡涛,杨金来,等. 异长叶烷基噻唑类化合物的合成及其生物活性[J]. 南京林业大学学报（自然科学版）, 2017, 60(01): 149-155.

RUI Jian, CAI Tao, YANG Jinlai, YANG Yiqin, XU Xu, WANG Shifa. Synthesis and bioactivities evaluation of isolongifolanyl thiazole derivatives[J].Journal of Nanjing Forestry University (Natural Science Edition), 2017, 60(01): 149-155.DOI: 10.3969/j.issn.1000-2006.2017.01.023.

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异长叶烷基噻唑类化合物的合成及其生物活性

Synthesis and bioactivities evaluation of isolongifolanyl thiazole derivatives

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