华侨大学学报(自然科学版)
華僑大學學報(自然科學版)
화교대학학보(자연과학판)
JOURNAL OF HUAQIAO UNIVERSITY(NATURAL SCIENCE)
2015年
3期
309-313
,共5页
王立强%雷春花%邱飞%杨会勇
王立彊%雷春花%邱飛%楊會勇
왕립강%뢰춘화%구비%양회용
萘甲酰胺衍生物%受体酪氨酸激酶%抗肿瘤活性%分子对接
萘甲酰胺衍生物%受體酪氨痠激酶%抗腫瘤活性%分子對接
내갑선알연생물%수체락안산격매%항종류활성%분자대접
naphthamide derivatives%receptor tyrosine kinase%anti-tumor activity%molecular docking
合成一系列萘甲酰胺衍生物,初步筛选出先导化合物TW918,测定其对肿瘤细胞的活性影响,考察其与激酶分子EGFR的结合性及对 EGFR 蛋白表达的影响.TW918结构经1 H-NMR,13 C-NMR 和 HR-MS 表征确证.实验结果表明:TW918对四种肿瘤细胞均有一定的抑制活性,但对正常细胞的影响较小;分子对接显示TW918能以母核喹啉为头,深入占据到EGFR的活性口袋中,并与活性残基形成氢键,其最低自由结合能为-46.1 kJ·mol-1;TW918能以剂量依赖性方式明显抑制四种肿瘤细胞中EGFR蛋白的表达.
閤成一繫列萘甲酰胺衍生物,初步篩選齣先導化閤物TW918,測定其對腫瘤細胞的活性影響,攷察其與激酶分子EGFR的結閤性及對 EGFR 蛋白錶達的影響.TW918結構經1 H-NMR,13 C-NMR 和 HR-MS 錶徵確證.實驗結果錶明:TW918對四種腫瘤細胞均有一定的抑製活性,但對正常細胞的影響較小;分子對接顯示TW918能以母覈喹啉為頭,深入佔據到EGFR的活性口袋中,併與活性殘基形成氫鍵,其最低自由結閤能為-46.1 kJ·mol-1;TW918能以劑量依賴性方式明顯抑製四種腫瘤細胞中EGFR蛋白的錶達.
합성일계렬내갑선알연생물,초보사선출선도화합물TW918,측정기대종류세포적활성영향,고찰기여격매분자EGFR적결합성급대 EGFR 단백표체적영향.TW918결구경1 H-NMR,13 C-NMR 화 HR-MS 표정학증.실험결과표명:TW918대사충종류세포균유일정적억제활성,단대정상세포적영향교소;분자대접현시TW918능이모핵규람위두,심입점거도EGFR적활성구대중,병여활성잔기형성경건,기최저자유결합능위-46.1 kJ·mol-1;TW918능이제량의뢰성방식명현억제사충종류세포중EGFR단백적표체.
To synthesize a series of naphthamide derivatives and screen out one lead compound TW918,this paper studys its anti-tumor activity invitro,and investigats its ability to bind with kinase and the effect on the expression of EGFR protein.1 H-NMR,13 C-NMR and HR-MS confirmed the structure of TW918.The results of MTT assay showed that TW918 had certain inhibitory effects against four types of tumor cells,but had less effects on normal cells.Molecular docking revealed that TW918 could make use of the quinoline as head to occupy the activity pocket of EGFR deeply,and form hydrogen bonds with the active residues of EGFR around it,whose lowest free binding energy was -46 .1 kJ · mol-1 .Western Blot demonstrated that TW918 could inhibit the expression of EGFR in all four types of tumor cells in a dose-dependent manner significantly.