含氮杂环甾体化合物的抗肿瘤活性研究进展

doi:10.3969/j.issn.1004-616x.2018.04.015

癌变·畸变·突变 ›› 2018, Vol. 30 ›› Issue (4): 318-325.doi: 10.3969/j.issn.1004-616x.2018.04.015

含氮杂环甾体化合物的抗肿瘤活性研究进展

蔡晓锐¹, 朱志伟¹, 朱辉德¹, 蔡奋¹, 许斯琪¹, 陈一村²

1. 汕头大学医学院附属肿瘤医院, 广东汕头 515041;
2. 汕头大学医学院药理学教研室, 广东汕头 515041

收稿日期:2017-11-16 修回日期:2018-04-12 出版日期:2018-07-30 发布日期:2018-07-30
通讯作者: 陈一村,E-mail:chenyicun@yeah.net E-mail:chenyicun@yeah.net
作者简介:蔡晓锐,E-mail:469497091@qq.com
基金资助:
广东省自然科学基金资助项目（2015A030313432）；广东省协同创新与平台环境建设资助项目（2016B090918129）；汕头市科技计划项目（汕府科[2015]132号）

Received:2017-11-16 Revised:2018-04-12 Online:2018-07-30 Published:2018-07-30

摘要/Abstract

摘要： 在甾体的甾核或者支链上引入不同的官能团后可以得到不同生理活性的化合物，它们有可能会成为人类治疗不同疾病的药物。甾体药物除了作为传统激素类药物使用外，在抗肿瘤药物中的应用也成为甾体的重要研究内容之一。含有氮杂环官能团的甾体化合物是一类具有显著生理活性的化合物。本文按照氮杂环基团在甾体母核中的不同取代位置而具备不同的抗肿瘤活性进行讨论，概述了近5年来新合成及新发现的氮杂环甾体化合物的设计、筛选，以及在抑制肿瘤细胞生长增殖活性方面的研究，并对其发展趋势和应用前景进行了展望。

关键词: 含氮杂环甾体化合物, 生物活性, 抗肿瘤活性, 甾体药物

中图分类号:

R965

蔡晓锐, 朱志伟, 朱辉德, 蔡奋, 许斯琪, 陈一村. 含氮杂环甾体化合物的抗肿瘤活性研究进展[J]. 癌变·畸变·突变, 2018, 30(4): 318-325.

参考文献

[1] MOHAMED N R,ELMEGEED G A. ABD-ELMALEK H A,et al. Synthesis of biologically active steroid derivatives by the utility of Lawesson's reagent[J]. Steroids,2005,70(3):131-136.
[2] Al-MASOUDI N A,MAHDI K M,ABDUL-RIDA N A,et al. A new pregnenolone analogues as privileged scaffolds in inhibition of CYP17 hydroxylase enzyme. Synthesis and in silico molecular docking study[J]. Steroids,2015,100:52-59.
[3] LEI M,XIAO Z,MA B,et al. Synthesis and biological evaluation of bufalin-3-yl nitrogen-containing-carbamate derivatives as anticancer agents[J]. Steroids,2016,108:56-60.
[4] SZABO J,PATAKI Z,WOLFLING J,et al. Synthesis and biological evaluation of 13α-estrone derivatives as potential antiproliferative agents[J]. Steroids,2016,113:14-21.
[5] UZZAMAN S,SIDDIQUI T,ALAM M C,et al. Synthesis,characterization and anticancer studies of new steroidal oxadiazole,pyrrole and pyrazole derivatives[J]. J Saudi Chem Soc,2015,19:387-391.
[6] YU B,QI P P,SHI X J,et al. Efficient synthesis of new antiproliferative steroidal hybrids using the molecular hybridization approach[J]. Eur Med Chem,2016,117:241-255.
[7] 黄燕敏,戚斌斌,崔建国,等. 某些B-降胆甾噻唑化合物的合成及抗肿瘤活性研究[J]. 有机化学,2016,36:1602-1610.
[8] UZZAMAN S,ASIF M,ALI A,et al. Design,synthesis and biological evaluation of steroidal tetrazoles as antiproliferative and antioxidant agents[J]. Eur Chem Bull,2014,3(11):1075-1080.
[9] LOPES S M,SOUSA E P,BARREIRA L,et al. Synthesis and anti-cancer activity of chiral tetrahydropyrazolo[1,5-α] pyridine-fused steroids[J]. Steroids,2017,122:16-23.
[10] AGARWAL D S,ANANARAJU H S,SRIRAM D,et al. Synthesis,characterization and biological evaluation of bile acid-aromatic/heteroaromatic amides linked via amino acids as anti-cancer agents[J]. Steroids,2016,107:87-97.
[11] BANDAY A H,GIRI A K,PARVEEN R,et al. Design and synthesis of D-ring steroidal isoxazolines and oxazolines as potential antiproliferative agents against LNCaP,PC-3 and DU-145 cells[J]. Steroids,2014,87(9):93-98.
[12] BANDAY A H,SHAMEEM S A,JEELANI S. Steroidal pyrazolines and pyrazoles as potential 5α-reductase inhibitors:Synthesis and biological evaluation[J]. Steroids,2014,92:13-19.
[13] FAN N J,HE Q R,DUAN M,et al. Synthesis and antiproliferative activity of D-ring substituted steroidal benzamidothiazoles[J]. Steroids,2016,112:103-108.
[14] FAN N J,TANG J J,LI H,et al. Synthesis and cytotoxic activity of some novel steroidal C-17 pyrazolinyl derivatives[J]. Eur J Med Chem,2013,69(15):182-190.
[15] MERNYAK E,KOVACS I,MINORICS R,et al. Synthesis of trans-16-triazolyl-13α-methyl-17-estradiol diastereomers and the effects of structural modifications on their in vitro antiproliferative activities[J]. J Steroid Biochem Mol Biol,2015,150:123-134.
[16] ZHANG B L,ZHANG E,PANG L P,et al. Design and synthesis of novel D-ring fused steroidal heterocycles[J]. Steroids,2013,78(12/13):1200-1208.
[17] CONNER K P,VENNAM P,WOODS C M,et al. 1,2,3-Triazole-heme interactions in cytochrome P450:Functionally competent triazole-water-heme complexes[J]. Biochemistry,2012,51(32):6441-6457.
[18] RASSOKHINA I V,VOLKOVA Y A,KOZLOV A S,et al. Synthesis and antiproliferative activity evaluation of steroidal imidazo[1,2-α] pyridines[J]. Steroids,2016,113:29-37.
[19] ARENAS-GONZALEZ A,MENDEZ-DELGADO L A,MERINO-MONTIEL P,et al. Synthesis of monomeric and dimeric steroids containing[1,2,4] triazolo[1,5-α]pyrimidines[J]. Steroids,2016,116:13-19.
[20] YU B,SUN X N,SHI X J,et al. Efficient synthesis of novel antiproliferative steroidal spirooxindoles via the[3+2] cycloaddition reactions of azomethine ylides[J]. Steroids,2015,102:92-100.
[21] LI J,HUO H,GUO R,et al. Facile and efficient access to Androsten-17-(1',3',4') -pyrazoles and Androst-17β-(1',3',4') -pyrazoles via Vilsmeier reagents,and their antiproliferative activity evaluationin vitro[J]. Eur J Med Chem,2017,130:1-14.
[22] SILVA-ORTIZ A V,BRATOEFF E,RAMIREZ-APAN M T,et al. Synthesis and biological activity of two pregnane derivatives with a triazole or imidazole ring at C-21[J]. J Steroid Biochem,2016,159:8-18.
[23] YU B,SHI X,ZHENG Y,et al. A novel[1,2,4] triazolo[1,5-α] pyrimidine-based phenyl-linked steroid dimer:Synthesis and its cytotoxic activity[J]. Eur J Med Chem,2013,69:323-330.
[24] BJEDOV S,JAKIMOV D,PILIPOVIC A,et al. Antitumor activity of newly synthesized oxo and ethylidene derivatives of bile acids and their amides and oxazolines[J]. Steroids,2017,120:19-25.
[25] FRANK E,KOVACS D,SCHNEIDER G,et al. Synthesis of novel steroidal 16-spiroisoxazolines by 1,3-dipolar cycloaddition,and an evaluation of their antiproliferative activities in vitro[J]. Mol Divers,2014,18(3):521-534.
[26] KUZIKOV A V,DUGIN N,STULOV S,et al. Novel oxazolinyl derivatives of pregna-5,17(20)-diene as 17α-hydroxylase/17,20-lyase (CYP17A1) inhibitors[J]. Steroids,2014,88:66-71.
[27] BANDAY A H,MIR B P,LONE I H,et al. Studies on novel D-ring substituted steroidal pyrazolines as potential anticancer agents[J]. Steroids,2010,75(12):805-809.
[28] IVANYI Z,SZABO N,HUBER J,et al. Synthesis of D-ring-substituted(5'R)-and(5'S)-17β-pyrazolinylandrostene epimers and comparison of their potential anticancer activities[J]. Steroids,2012,77(5):566-574.
[29] MOHAREB R M,EL-SAYED N N,ABDELAZIZ M A. The Knoevenagel reactions of pregnenolone with cyanomethylene reagents:Synthesis of thiophene,thieno[2,3-b]pyridine,thieno[3,2-d] isoxazole derivatives of pregnenolone and their in vitro cytotoxicity towards tumor and normal cell lines[J]. Steroids,2013,78(12-13):1209-1219.
[30] 崔建国,赵丹丹,何冬梅,等. 去氢表雄酮噻唑衍生物的合成及抗肿瘤活性评估[J]. 有机化学,2016,36:630-637.
[31] 何冬梅,刘亮,郑嘉桦,等. 具有吡唑啉结构甾体芳杂环化合物的合成及抗肿瘤活性[J].中国药物化学杂志,2016,26(1):61-64.
[32] 韦英亮,姚秋翠,杨春晖,等. N-杂芳基鹅脱氧胆酰胺化合物的合成及抗肿瘤活性研究[J]. 化学研究与应用,2015,27(2):139-144.
[33] Bryce A,Ryan C J. Development and clinical utility of Abiraterone acetate as an androgen synthesis inhibitor[J].Clin Pharmacol Ther,2012,91(1):101-108.
[34] Vasaitis T S,Njar V C. Novel,potent anti-androgens of therapeutic potential:recent advances and promising developments[J]. Future Med. Chem,2010,2(4):667-680.

含氮杂环甾体化合物的抗肿瘤活性研究进展

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 2

编辑推荐

Metrics

本文评价

[1]	周雯;李慧;陈敏. 生物活性肽粉的急性毒性和致突变性试验[J]. , 2009, 21(4): 306-308.
[2]	蔡唯佳1;马云青2;祁逸梅3;牛永东1;许丽艳1;李建新1,3,;李恩民1. 白桦酯醇对食管癌细胞EC109的抑制作用[J]. , 2006, 18(1): 16-018.