异长叶烯基噻唑类化合物的合成及其抑菌、抗肿瘤活性研究

doi:10.3969/j.issn.0253-2417.2016.06.007

林产化学与工业 ›› 2016, Vol. 36 ›› Issue (6): 41-48.doi: 10.3969/j.issn.0253-2417.2016.06.007

异长叶烯基噻唑类化合物的合成及其抑菌、抗肿瘤活性研究

芮坚¹, 杨金来¹, 蔡涛¹, 徐徐^1,2, 王石发^1,2

1. 南京林业大学化学工程学院, 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. 江苏省生物质能源与材料重点实验室, 江苏南京 210042

收稿日期:2015-11-19 出版日期:2016-12-25 发布日期:2016-12-23
通讯作者: 王石发,教授,博士生导师,主要从事手性合成研究;E-mail:wsfyyq@njfu.com.cn E-mail:wsfyyq@njfu.com.cn
作者简介:芮坚(1992-),男,江苏常州人,硕士生,主要从事天然产物的有机合成工作
基金资助:
江苏省高校自然科学研究重大项目（14KJA220001）；国家自然科学基金资助项目（31470592）；江苏省生物质能源与材料重点实验室开放基金（JSBEM2014010）

Synthesis of Isolongifolanyl Thiazole Compounds and Their Antibacterial and Antitumor Activities

RUI Jian¹, YANG Jin-lai¹, CAI Tao¹, XU Xu^1,2, WANG Shi-fa^1,2

1. College of Chemical Engineering, Jiangsu Key Laboratory of Biomass Green Fuels and Chemicals, Nanjing 210037, China;
2. Jiangsu Key Laboratory of Biomass Energy and Material, Nanjing 210042, China

Received:2015-11-19 Online:2016-12-25 Published:2016-12-23

摘要/Abstract

摘要： 以异长烯酮为原料，通过缩合、亲核取代和环化等手段合成了11种新型异长叶烯基噻唑类化合物，同时采用¹H NMR、¹³C NMR、LC-MS和FT-IR对化合物进行了鉴定，从而确定了化合物的结构。对目标化合物进行了抑菌活性实验，结果表明：（E）-4-（4-甲氧基苯基）-2-（2-（1，1，5，5-四甲基-3，4，5，6-四氢-1H-2，4a-亚甲基-7（2H）-亚基）肼基）噻唑（2e）与（E）-4-（4-甲基苯基）-2-（2-（1，1，5，5-四甲基-3，4，5，6-四氢-1H-2，4a-亚甲基-7（2H）-亚基）肼基）噻唑（2g）对细菌（大肠杆菌与金黄色葡萄球菌）具有较好的抑制效果，最低抑菌质量浓度（MIC）为7.8 mg/L。（E）-4-氯苯基-2-（2-（1，1，5，5-四甲基-3，4，5，6-四氢-1H-2，4a-亚甲基-7（2H）-亚基）肼基）噻唑（2b）对真菌（白念球菌与热带假丝酵母）抑制效果优于其他化合物，其MIC值为15.6 mg/L。采用噻唑蓝（MTT）法对目标化合物进行了人体肝癌细胞（HepG2）抗癌活性测试，化合物2g（IC₅₀=43.9±0.9 mg/L）对HepG2具有较好的抗癌活性。

关键词: 异长叶烯酮, 噻唑类化合物, 抗菌活性, 抗肝癌活性

Abstract: Eleven new kinds of isolongifolanyl thiazole compounds were synthesized by condensation, nucleophilic substitution and cyclization from isolongifolenone. The structures of the target compounds were characterized by ¹H NMR, ¹³C NMR, LC-MS and FT-IR, respectively. Antibacterial evaluation of the compounds was carried out by minimum inhibitory concentrations assay (MIC). The results showed that the antibacterial activities of (E)-4-(4-methoxyphenyl)-2-(2-(1,1,5,5-tetramethyl-3,4,5,6-tetrahydro-1H-2,4a-methanonaphthalen-7(2H)-ylidene)hydrazinyl)thiazole(2e) and (E)-2-(2-(1,1,5,5-tetramethyl-3,4,5,6-tetrahydro-1H-2,4a-methanonaphthalen-7(2H)-ylidene)hydrazinyl)-4-(p-tolyl) thiazole (2g) were better than those of others against Escherichia coli and Staphylococcus aureus. Their MIC were 7.8 mg/L. The antibacterial activity of (E)-4-(4-chlorophenyl)-2-(2-(1,1,5,5-tetramethyl-3,4,5,6-tetrahydro-1H-2,4a-methanonaphthalen-7(2H)-ylidene)hydrazinyl)thiazole (2b) was better than those of others against fungus. Its MIC value aganist Candida albicans and Candida tropicalis was 15.6 mg/L. Their antitumor activities against HepG2 were evaluated by thiazole blue test(MTT). Compound 2g (IC₅₀=43.9±0.9 mg/L) was found to be the most potent derivative overall the tested compounds against HepG2.

Key words: isolongifolenone, thiazole compounds, antibacterial activity, antitumor activity

中图分类号:

TQ35

芮坚, 杨金来, 蔡涛, 徐徐, 王石发. 异长叶烯基噻唑类化合物的合成及其抑菌、抗肿瘤活性研究[J]. 林产化学与工业, 2016, 36(6): 41-48.

RUI Jian, YANG Jin-lai, CAI Tao, XU Xu, WANG Shi-fa. Synthesis of Isolongifolanyl Thiazole Compounds and Their Antibacterial and Antitumor Activities[J]. Chemistry and Industry of Forest Products, 2016, 36(6): 41-48.

参考文献

[1] 彭晗,杨丽娟,徐徐,等.异长叶烯酮的绿色合成研究[J].林产化学与工业,2015,35(3):97-103. PENG Han,YANG Li-juan,XU Xu,et al.Green synthesis of isolongifolenone[J].Chemistry and Industry of Forest Products,2015,35(3):97-103.
[2] THIRUMURUGAN R,SRIRAM D,SAXENA A,et al.2,4-Dimethoxyphenylsemicarbazones with anticonvulsant activity against three animal models of seizures:Synthesis and pharmacological evaluation[J].Bioorganic & Medicinal Chemistry,2006,14(9):3106-3112.
[3] KHAN S A,KUMAR P,JOSHI R,et al.Synthesis and in vitro antibacterial activity of new steroidal thiosemicarbazone derivatives[J].European Journal of Medicinal Chemistry,2008,43(9):2029-2034.
[4] PANDYA D H,SHARMA J A,JALANI H B,et al.Novel thiazole-thiophene conjugates as adenosine receptor antagonists:Synthesis,biological evaluation and docking studies[J].Bioorganic & Medicinal Chemistry Letters,2015,25(6):1306-1309.
[5] 张静,康卓,李淼,等.具有生物活性的异噻唑类化合物研究进展[J].农药,2011,50(3):157-164. ZHANG Jing,KANG Zhuo,LI Miao,et al.The research progress of isothiazole compounds with bioactivities[J].Agrochemicals,2011,50(3):157-164.
[6] GHASEMI B,SANJARANI G,SANJARANI Z,et al.Evaluation of anti-bacterial effects of some novel thiazole and imidazole derivatives against some pathogenic bacteria[J].Iranian Journal of Microbiology,2015,7(5):281-286.
[7] DAWOOD K M,ELDEBSS T M A,EL-ZAHABI H S A,et al.Synthesis of some new pyrazole-based 1,3-thiazoles and 1,3,4-thiadiazoles as anticancer agents[J].European Journal of Medicinal Chemistry,2013,70:740-749.
[8] ALI A R,El-BENDARY E R,GHHALY M A,et al.Synthesis,in vitro anticancer evaluation and in silico studies of novel imidazo[2,1-b] thiazole derivatives bearing pyrazole moieties[J].European Journal of Medicinal Chemistry,2014,75:492-500.
[9] HELAL M H M,SALEM M A,EL-GABY M S A,et al.Synthesis and biological evaluation of some novel thiazole compounds as potential anti-inflammatory agents[J].European Journal of Medicinal Chemistry,2013,65:517-526.
[10] HOLLA B S,MALINI K V,RAO B S,et al.Synthesis of some new 2,4-disubstituted thiazoles as possible antibacterial and anti-inflammatory agents[J].European Journal of Medicinal Chemistry,2003,38(3):313-318.
[11] WANG Ning-yu,XU Ying,ZUO Wei-xiong,et al.Discovery of imidazo[2,1-b] thiazole HCV NS4B inhibitors exhibiting synergistic effect with other direct-acting antiviral agents[J].Journal of Medicinal Chemistry,2015,58(6):2764-2778.
[12] EL-SABBAGH O I,BARAKA M M,IBRAHIM S M,et al.Synthesis and antiviral activity of new pyrazole and thiazole derivatives[J].European Journal of Medicinal Chemistry,2009,44(9):3746-3753.
[13] 严曼,石德清,肖琳霞.新型N-(4,6-二取代嘧啶-2-基)-1-[取代吡啶(噻唑)甲基]-5-甲基-1H-1,2,3-三唑基-4-甲酰胺的合成与除草活性[J].有机化学,2008,28(6):1012-1015. YAN Man,SHI De-qing,XIAO Lin-xia.Synthesis and herbicidal activity of novel N-(4,6-disubstituted pyrimidin-2-yl)-1-[substitutedpyridyl(thiazolyl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxamides[J].Chinese Journal of Organic Chemistry,2008,28(06):1012-1015.
[14] DAI H,XIAO Y S,LI Z,et al.The thiazoylmethoxy modification on pyrazole oximes:Synthesis and insecticidal biological evaluation beyond acaricidal activity[J].Chinese Chemical Letters,2014,25(7):1014-1016.
[15] O'HALLORAN D M,BURNELL A M.An investigation of chemotaxis in the insect parasitic nematode Heterorhabditis bacteriophora[J].Parasitology,2003,127(04):375-385.
[16] YU Hai-bo,QIN Zhen-feng,DAI Hong,et al.Synthesis and insecticidal activity of N-substituted (1,3-thiazole) alkyl sulfoximine derivatives[J].Journal of Agricultural and Food Chemistry,2008,56(23):11356-11360.

异长叶烯基噻唑类化合物的合成及其抑菌、抗肿瘤活性研究

Synthesis of Isolongifolanyl Thiazole Compounds and Their Antibacterial and Antitumor Activities

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