Rakicidin B1酯化衍生物的体外抗肿瘤和抗菌活性

Antitumor and antibacterial activities of esterified derivatives of rakicidin B1

目的本研究对rakicidin B1化合物3位羟基进行结构修饰,得到rakicidin B1酯化反应的系列衍生物,并考察其体外抗肿瘤及抗菌活性。方法以rakicidin B1为原料,经与不同的氯甲酸酯反应,再经水洗、制备、冻干制得目标化合物,其结构经~1H NMR,HR-ESI-MS确证。结果对酯化反应的4个衍生物进行体外抗肿瘤及抗菌活性测定,结果表明,化合物1~4对常氧和乏氧培养下的人结肠癌细胞HCT-8和人胰腺癌细胞PANC-1均具有较好的体外抑制作用;总体上看化合物对耐甲氧西林金黄色葡萄球菌、艰难梭菌和万古霉素耐药粪肠球菌等10株革兰阳性菌活性均低于对照品,活性较弱。结论化合物1和3对人结肠癌细胞HCT-8和人胰腺癌细胞PANC-1具有较强的乏氧抗肿瘤活性,可作为新型的抗癌备选药物进行进一步研究。

Objective To develop a synthetic method that enables efficient synthesis of rakicidin B1 derivatives and to investigate their antitumor and antibacterial activities in vitro.Methods The target products were synthesized by reaction with different chloroformic acid esters through esterification,washing,preparation,and freeze-drying,and their structures were confirmed by^1H NMR and HR-ESI-MS analyses.Results The antitumor and antibacterial activities of four esterification derivatives were measured in vitro.The results showed that compounds 1~4 had good inhibitory effects against HCT-8 and PANC-1 human tumor cell lines under the hypoxic and normoxic conditions.Nevertheless,the activities of the compounds 1~4 against 10 strains of Gram-positive bacteria,including methicillinresistant Staphylococcus aureus,Clostridium difficile,and vancomycin resistant Enterococcus faecalis,were lower than the positive control.Conclusion Compounds 1 and 3 have strong activities against HCT-8 and PANC-1 human tumor cell lines under the hypoxic conditions and can be used as new anticancer drugs for further research.