Evaluation on in vitro anticancer effect against cancer cells and toxicity in vivo of phenanthroimidazole derivatives on zebrafish embryos

Abstract

Objective To design and synthesize phenanthroimidazole derivatives L271, and to evaluate in vitro antitumor activity and toxicity in vivo of phenanthroimidazole derivatives on zebrafish embryos. Methods Using 1,10-phenanthroline-5,6-dione and 2-methylbenzaldehyde as raw material, phenanthroimidazole derives L271 was prepared by microwave-assisted synthesis technology. The inhibition effects of phenanthroimidazole derivatives L271 on the growth of human cervical cancer cells Hela and human lung adenocarcinoma cells A549 were detected by MTT assay. With zebrafish embryos as a model, the effects of phenanthroimidazole derivatives L271 on the morphology, hatching rates, mortality rates, and malformation rates of zebrafish embryos were investigated to study acute toxicity. Results The chemical structure of target compound L271 was characterized by ESI-MS. Phenanthroimidazole derives L271 showed anti-proliferation effect on human cervical cancer Hela cells and human lung adenocarcinoma A549 cells cultured in vitro, especially for human cervical cancer Hela cells. The inhibitory activity (IC50) of L271 against human cervical cancer Hela cells was about (8.38±0.09)μmol/L, which was close to pirarubicin [IC50 = (6.97±0.07)μmol/L] at the same conditions. Compared with control groups, several abnormalities caused by L271 at ≥15μmol/L were observed including caudal fin atrophy, spinal curvature, yolk sac edema, pericardial edema, tail bending and etc. . When the concentration of L271 was equal or great than 30μmol/L, hatching rates of zebrafish embryos were reduced significantly, while mortality rates were increased significantly (P<0.05). The median lethal concentration (LC50) of L271 on zebrafish embryos at 48, 72, 96 hpf were 37.331μmol/L(95%CI: 35.535-39.301)、34.911μmol/L(95%CI: 33.213-36.7290)、30.283μmol/L(95%CI: 29.590-30.980), respectively. When the concentration of L271 was equal or great than 15μmol/L, the percentage of normal reduced, and the percentage of mortality increased, while the percentage of mortality increased firstly and then decreased as the concentration of L271 increased. Conclusion L271 exhibit considerable inhibitory effects on human cervical cancer cells Hela, which is comparable to that of pirarubicin. And no obvious toxic effects of L271 on zebrafish embryo when the concentration of L271 is less than 10μmol/L. Key words: Phenanthroimidazole derivatives; Antitumor activity; Zebrafish; Toxicity