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目的:对29个全新长春氟宁衍生物进行体内、外药效筛选,以期发现具有开发前景的抗肿瘤化合物。方法:体外筛选采用SRB法,移植人非小细胞肺癌A549裸小鼠模型作为体内药效模型。结果:通过体外IC50结果,结合化学结构,挑选出2个较有优势化合物:SHR115706和SHR115766,IC50分别为0.05和0.29μmol.L-1。SHR115706能够剂量依赖性的抑制裸鼠移植肿瘤的生长,抗癌疗效与长春氟宁相当;SHR115766亦可抑制肿瘤的生长,但剂量依赖性不明显。SHR115706(80 mg.kg-1),SHR115766(80 mg.kg-1)和长春氟宁(35 mg.kg-1,作为阳性对照)组肿瘤增殖速率分别为47.5%,57.6%和46.5%。SHR115706和SHR115766对裸鼠表现的毒性均明显低于长春氟宁。结论:SHR115706有望成为抗肿瘤新药。
OBJECTIVE: To screen 29 new vinflunine derivatives in vitro and in vivo for the purpose of discovering promising anti-tumor compounds. Methods: SRB method was used in vitro to screen human lung cancer A549 non-small cell lung cancer model as in vivo efficacy model. RESULTS: Two IC50s, SHR115706 and SHR115766, with IC50 of 0.05 and 0.29μmol.L-1, were selected by IC50 in vitro and chemical structure. SHR115706 can inhibit the growth of nude mice transplanted tumor in a dose-dependent manner, and the anti-cancer effect is comparable to that of vinflunine. SHR115766 also can inhibit tumor growth, but the dose-dependent manner is not obvious. The tumor proliferation rates of SHR115706 (80 mg.kg-1), SHR115766 (80 mg.kg-1) and vinflunine (35 mg.kg-1 as positive control) were 47.5%, 57.6% and 46.5%, respectively. The toxicity of SHR115706 and SHR115766 to nude mice were significantly lower than that of vinflunine. Conclusion: SHR115706 is expected to become a new antitumor drug.