CAJ | 학술논문

以4,5-二甲氧基-2-氨基苯甲酸和醋酸甲脒为原料,经环化、氯化、胺化和缩合反应,合成了15个新的喹唑啉哌嗪缩氨基硫脲衍生物,其结构经1 H NMR,13 C NMR, HRMS及元素分析确认.采用MTT法测试了化合物6a~6o对表皮生长因子受体(EGFR)过度表达的人乳腺癌MCF-7、人肺癌A549和人前列腺癌PC3的体外抗癌活性.结果表明,部分化合物表现出较强的抗癌活性,其中,化合物6a和6o对3种癌细胞的抗癌活性优于对照药拉帕替尼(Lapatinib),略低于对照药阿霉素(ADM).化合物6a和6o对MCF-7的IC50值分别为6.97和6.99μmol/L,对A549的IC50值分别为5.15和3.11μmol/L,而对PC3的IC50值分别为2.30和1.42μmol/L.本文还初步探讨了化合物结构与抗癌活性之间的关系.
이4,5-이갑양기-2-안기분갑산화작산갑미위원료,경배화、록화、알화화축합반응,합성료15개신적규서람고진축안기류뇨연생물,기결구경1 H NMR,13 C NMR, HRMS급원소분석학인.채용MTT법측시료화합물6a~6o대표피생장인자수체(EGFR)과도표체적인유선암MCF-7、인폐암A549화인전렬선암PC3적체외항암활성.결과표명,부분화합물표현출교강적항암활성,기중,화합물6a화6o대3충암세포적항암활성우우대조약랍파체니(Lapatinib),략저우대조약아매소(ADM).화합물6a화6o대MCF-7적IC50치분별위6.97화6.99μmol/L,대A549적IC50치분별위5.15화3.11μmol/L,이대PC3적IC50치분별위2.30화1.42μmol/L.본문환초보탐토료화합물결구여항암활성지간적관계.
To find new EGFR inhibitors, 15 novel quinazoline derivatives containing thiosemicarbazone struc-ture were designed and synthesized from 2-amino-4 ,5-dimethoxybenzoic acid and formamidine acetate by the cyclization, chlorination, amination and condensation reactions. All structures of target compounds were con-firmed by 1 H NMR,13 C NMR, HRMS and elemental analysis. The in vitro anticancer activities of compounds 6a—6o against EGFR over-expressing of MCF-7(Human breast cancer), A549(Human pulmonary adenocar-cinoma) and PC3(Human prostate cancer) cell lines were tested using colorimetric MTT assay. The results indicated that several compounds showed potent activity. Compounds 6a and 6o were more potent than Lapa-tinib, but slightly weaker than ADM against the three cell lines. The IC50 values of compounds 6a and 6o against MCF-7 cell line were 6. 97 and 6. 99 μmol/L, against A549 were 5. 15 and 3. 11 μmol/L and against PC3 were 2. 30 and 1. 42μmol/L, respectively. Preliminary structure-activity relationship was also discussed.