双(3-吗啉丙氧基)姜黄素抗肿瘤活性研究

Antitumor Activity of Bis(3-morpholinopropoxy) Curcumin

合成双(3-吗啉丙氧基)姜黄素(PR1),研究PR1体内外抗肿瘤活性。姜黄素与N-(3-氯丙基)吗啉反应制备PR1,MTT法评价PR1体外对人肾癌细胞OS-RC-2、786-O和人慢性粒细胞白血病耐药细胞KA的抑制增殖活性,考察PR1体内抑制人结肠癌HT29裸鼠移植性肿瘤活性。PR1体外对肾癌细胞OS-RC-2和786-O抑制活性比姜黄素强,而对白血病耐药细胞KA抑制活性比姜黄素差。PR1体内对BALB/C-nu小鼠HT29皮下移植瘤的抑制作用明显,100 mg/kg·d灌胃的抑制率为55.7%,差别具有显著性(P<0.01),对裸鼠的体重无明显影响。PR1在体内外均有较强抗肿瘤活性。

The objectives of this study were to synthesize bis （3-morpholinopropoxy）eurcumln （PR1） and to evaluate its antitumor activity. PR1 was synthesized from curcumln and N-（3-chlompropyl） morpholine. The in vitro antitumor activities of PR1 was evaluated through MTF assays against gastric carcinoma ceils （ OS-RC-2 and 786-O） and chronic myelogenous leukemia resistance cell （KA）. The in vivo antitumor activities of PR1 were evaluated by its growth inhibition of human colon cancer HT29 tumor xenograft in BALB/C-nu nude mice. Compared with curcumln, PR1 showed improved activities against OS-RC-2,786-0 ceUs, while less activities against KA cell. PR1 showed remarkable in vivo tumor growth inhibition activity. A dose of 100 mg/kg . d was able to inhibit the growth of HT29 xenograft in BALB/C-nu nude mice by 55.7%. No obvious decrease on the body weight of tested nude mice was observed. In concluslon,PR1 showed obvious antltumor activities both in vitro and in vivo.