| 第 52 卷第 2 期 |  | Vol. 52 No. 2 | | 2022 年 4 月 | Apr 2022 |
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所屬欄目：醫藥及中間體
6-氨基-4-苯胺喹唑啉骨架與5-氟尿嘧啶-1-乙酸拼接合成及抗腫瘤活性研究 |
| 梁光平1，田 芷1，梁光焰2，王道平2，楊 俊1*，李 敏1
（1.遵義醫藥高等專(zhuān)科學(xué)校 藥學(xué)系，貴州 遵義 563006；2.貴州省中國科學(xué)院天然產(chǎn)物化學(xué)重點(diǎn)實(shí)驗室，貴州 貴陽(yáng) 550014） |
| 摘 要：以2-氨基-5-硝基苯腈和三種鹵代苯胺為原料，通過(guò)縮合、環(huán)化、還原3步反應制得三種6-氨基-4-苯胺喹唑啉衍生物，再與5-氟尿嘧啶-1-乙酸通過(guò)酰胺化反應得到三種未見(jiàn)文獻報道的目標產(chǎn)物（8a~8c），其結構經(jīng)1H NMR和MS確認。利用MTT法考察化合物8a~8c對HepG2、A549、Hela、MCF-7、A549/DDP細胞的抑制活性，利用ELISA法檢測化合物8a~8c對A549細胞上清液中EGFR酶的抑制作用。結果表明，化合物8a~8c對五種細胞都具有一定的抑制作用，化合物8a對HepG2、A549、A549/DDP細胞的抑制作用分別是厄洛替尼的1.85、1.47、2.07倍，對MCF-7、Hela細胞的IC50分別為1.98、18.71 μmol/L。 |
| 關(guān)鍵詞：5-氟尿嘧啶；喹唑啉；合成；抗腫瘤 |
| 中圖分類(lèi)號：R914.5 文獻標識碼：A 文章編號：1009-9212（2022）02-0020-04 |
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| Splicing of 6-Amino-4-anilinoquinazoline with 5-Fluorouracil-1-acetic Acid and Its Antitumor Activity |
| LIANG Guang-ping1, TIAN Zhi1, LIANG Guang-yan2, WANG Dao-ping2, YANG Jun1*, LI Min1
(1. Department of Pharmacy, Zunyi Medical and Pharmaceutical College, Zunyi 563006, China; 2.The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550014, China) |
| Abstract：Three 6-amino-4-phenylamine quinazoline derivatives were synthesized from 2-amino-5-nitrobenzonitrile and three aniline derivatives through a series of reactions including condensation, cyclization and reduction. Subsequently, three target ligands (8a~8c) were obtained through amidation reactions between 5-fluorouracil-1-acetic acid and the 6-amino-4-phenylamine quinazoline derivatives. Their structures were confirmed by 1H NMR and MS. The inhibitory activity of compound 8a~8c on HepG2, A549, Hela, MCF-7 and A549/DDP cells was investigated by MTT Assay while the inhibitory effects of compounds 8a~8c on EGFR enzyme were investigated by ELISA. The results showed that compound 8a~8c had a certain inhibitory effect on five kinds of cells, and the inhibitory effects of compound 8a on HepG2, A549 and A549/DDP were 1.85, 1.47 and 2.07 times that of Erlotinib, and the IC50 on MCF-7 and Hela were 1.98 and 18.71 μmol/L, respectively. |
| Key words：5-fluorouracil; quinazoline; synthesis; anti-tumor |
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基金項目：貴州省科學(xué)技術(shù)基金資助項目（黔科合基礎［2019］1356號），遵義醫藥高等專(zhuān)科學(xué)校博士科研啟動(dòng)項目（遵醫專(zhuān)科合BS2018001號）。
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作者簡(jiǎn)介：梁光平（1988—），男，貴州遵義人，副教授，博士，研究方向：化學(xué)成分的結構修飾及其活性研究（E-mail:guangping_liang@aliyun.com）。
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聯(lián) 系 人：楊 俊，講師，研究方向：合成藥物化學(xué)（E-mail:420625539@qq.com）。
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收稿日期：2022-02-09
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