{"title":"b -去甲胆固醇-6-酰胺类化合物的合成及抗增殖活性评价。","authors":"Yanmin Huang, Zining Peng, Chang Liu, Chunling Pang, Sijing Chen, Chunfang Gan, Zhiping Liu, Jianguo Cui","doi":"10.2174/1573406419666230117101950","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The structure modification of steroids is commonly used to change the biological activity of steroids in medicinal chemistry. In recent years, it has been found that some derivatives derived from the structural modification of cholesterol display good inhibitory activity against tumor cell proliferation in vitro</i>.</p><p><strong>Methods: </strong>Using cholesterol as the starting material, different types of B-norcholesterol-6-amide derivatives were synthesized by the reaction of 6-carboxyl-B-norcholesterol with different alkyl amines or 6-amino-B-norcholesterol with different acyl chlorides. The inhibitory activity of compounds on the proliferation of tumor cell lines was investigated by the MTT method.</p><p><strong>Results: </strong>The results showed that the B-norcholesterol-6-amide compounds displayed distinct cytotoxicity against Sk-Ov-3 cells but caused no obvious damage against HEK-293T cells. Additionally, the steroidal amide derivatives formed from 6-amino-B-norcholesterol showed stronger cytotoxicity than those produced from 6-carboxyl-B-norcholesterol. Specially, compounds with chloroalkyl structure displayed significant inhibitory activity against all tumor cells tested. Among them, compounds 19-21 showed cytotoxicity like 2-methoxyestradiol as a positive control, and the IC</i><sub>50</sub> value of compound 20 on HeLa cells was 3.9 μM.</p><p><strong>Conclusion: </strong>After introducing chloroalkyl acyl groups into 6-position of 6-amino-B-norcholesterol, the cytotoxicity of resulting B-norcholesterol-6-amide compounds can be greatly enhanced.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis and Antiproliferative Activity Evaluation of B-norcholesterol-6- amide Compounds.\",\"authors\":\"Yanmin Huang, Zining Peng, Chang Liu, Chunling Pang, Sijing Chen, Chunfang Gan, Zhiping Liu, Jianguo Cui\",\"doi\":\"10.2174/1573406419666230117101950\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The structure modification of steroids is commonly used to change the biological activity of steroids in medicinal chemistry. In recent years, it has been found that some derivatives derived from the structural modification of cholesterol display good inhibitory activity against tumor cell proliferation in vitro</i>.</p><p><strong>Methods: </strong>Using cholesterol as the starting material, different types of B-norcholesterol-6-amide derivatives were synthesized by the reaction of 6-carboxyl-B-norcholesterol with different alkyl amines or 6-amino-B-norcholesterol with different acyl chlorides. The inhibitory activity of compounds on the proliferation of tumor cell lines was investigated by the MTT method.</p><p><strong>Results: </strong>The results showed that the B-norcholesterol-6-amide compounds displayed distinct cytotoxicity against Sk-Ov-3 cells but caused no obvious damage against HEK-293T cells. Additionally, the steroidal amide derivatives formed from 6-amino-B-norcholesterol showed stronger cytotoxicity than those produced from 6-carboxyl-B-norcholesterol. Specially, compounds with chloroalkyl structure displayed significant inhibitory activity against all tumor cells tested. Among them, compounds 19-21 showed cytotoxicity like 2-methoxyestradiol as a positive control, and the IC</i><sub>50</sub> value of compound 20 on HeLa cells was 3.9 μM.</p><p><strong>Conclusion: </strong>After introducing chloroalkyl acyl groups into 6-position of 6-amino-B-norcholesterol, the cytotoxicity of resulting B-norcholesterol-6-amide compounds can be greatly enhanced.</p>\",\"PeriodicalId\":18382,\"journal\":{\"name\":\"Medicinal Chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Medicinal Chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/1573406419666230117101950\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/1573406419666230117101950","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
摘要
背景:类固醇的结构修饰是药物化学中常用的改变类固醇生物活性的方法。近年来，人们发现一些由胆固醇结构修饰衍生的衍生物在体外对肿瘤细胞增殖表现出良好的抑制活性。方法:以胆固醇为原料，通过6-羧基- b -去胆固醇与不同的烷基胺或6-氨基- b -去胆固醇与不同的酰基氯化物反应合成不同类型的b -去胆固醇-6-酰胺衍生物。用MTT法研究了化合物对肿瘤细胞增殖的抑制作用。结果:b -去甲胆固醇-6-酰胺化合物对Sk-Ov-3细胞具有明显的细胞毒性，对HEK-293T细胞无明显损伤。此外，6-氨基- b -去胆固醇生成的甾体酰胺衍生物比6-羧基- b -去胆固醇生成的甾体酰胺衍生物具有更强的细胞毒性。特别地，含有氯烷基结构的化合物对所有肿瘤细胞都有明显的抑制活性。其中化合物19-21与阳性对照2-甲氧基雌二醇一样具有细胞毒性，化合物20对HeLa细胞的IC50值为3.9 μM。结论:在6-氨基- b -去甲胆固醇的6位引入氯烷基酰基后，所得到的b -去甲胆固醇-6-酰胺化合物的细胞毒性可显著增强。
Synthesis and Antiproliferative Activity Evaluation of B-norcholesterol-6- amide Compounds.
Background: The structure modification of steroids is commonly used to change the biological activity of steroids in medicinal chemistry. In recent years, it has been found that some derivatives derived from the structural modification of cholesterol display good inhibitory activity against tumor cell proliferation in vitro.
Methods: Using cholesterol as the starting material, different types of B-norcholesterol-6-amide derivatives were synthesized by the reaction of 6-carboxyl-B-norcholesterol with different alkyl amines or 6-amino-B-norcholesterol with different acyl chlorides. The inhibitory activity of compounds on the proliferation of tumor cell lines was investigated by the MTT method.
Results: The results showed that the B-norcholesterol-6-amide compounds displayed distinct cytotoxicity against Sk-Ov-3 cells but caused no obvious damage against HEK-293T cells. Additionally, the steroidal amide derivatives formed from 6-amino-B-norcholesterol showed stronger cytotoxicity than those produced from 6-carboxyl-B-norcholesterol. Specially, compounds with chloroalkyl structure displayed significant inhibitory activity against all tumor cells tested. Among them, compounds 19-21 showed cytotoxicity like 2-methoxyestradiol as a positive control, and the IC50 value of compound 20 on HeLa cells was 3.9 μM.
Conclusion: After introducing chloroalkyl acyl groups into 6-position of 6-amino-B-norcholesterol, the cytotoxicity of resulting B-norcholesterol-6-amide compounds can be greatly enhanced.
期刊介绍：
Aims & Scope
Medicinal Chemistry a peer-reviewed journal, aims to cover all the latest outstanding developments in medicinal chemistry and rational drug design. The journal publishes original research, mini-review articles and guest edited thematic issues covering recent research and developments in the field. Articles are published rapidly by taking full advantage of Internet technology for both the submission and peer review of manuscripts. Medicinal Chemistry is an essential journal for all involved in drug design and discovery.
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