Instituto Universitario de Bio-Orgánica Antonio González, Departamento de Química Orgánica, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez 2, 38206 La Laguna, Tenerife, Spain.
Bioorg Med Chem. 2013 May 1;21(9):2471-7. doi: 10.1016/j.bmc.2013.03.002. Epub 2013 Mar 14.
In the present study, a series of metallic complexes of the 1,4-naphthoquinone lawsone (2-6) were synthesized and evaluated for potential cytotoxicity in a mouse leukemic macrophagic RAW 264.7 cell line. Cell viability was determined by the MTT assay. Significant growth inhibition was observed for the copper complex (4) with an IC(50) value of 2.5 μM. This compound was selected for further evaluation of cytotoxic activity on several human cancer cells including HT-29 (human colorectal adenocarcinoma), HepG2 (human hepatocellular carcinoma) and HeLa, (human cervical adenocarcinoma cells). Significant cell viability decrease was also observed in HepG2 cells. The apoptotic potential of this complex was evaluated in these cells. Compound 4 induced apoptosis by a mechanism that involves the activation of caspases 3, 8 and 9 and modulation of apoptotic-related proteins such as Bax, Bad, and p53. These results indicate that metal complexes of lawsone derivatives, in particular compound 4, might be used for the design of new antitumoral agents.
在本研究中，我们合成了一系列 1,4-萘醌莱苏酮（2-6）的金属配合物，并在小鼠白血病巨噬细胞 RAW 264.7 细胞系中评估了它们的潜在细胞毒性。通过 MTT 法测定细胞活力。铜配合物（4）对细胞生长具有显著的抑制作用，IC50 值为 2.5 μM。选择该化合物进一步评估对几种人类癌细胞的细胞毒性活性，包括 HT-29（人结肠直肠腺癌）、HepG2（人肝癌）和 HeLa（人宫颈腺癌细胞）。在 HepG2 细胞中也观察到明显的细胞活力下降。评估了该复合物在这些细胞中的凋亡潜力。化合物 4 通过涉及激活 caspase 3、8 和 9 以及调节凋亡相关蛋白如 Bax、Bad 和 p53 的机制诱导细胞凋亡。这些结果表明，莱苏酮衍生物的金属配合物，特别是化合物 4，可能用于设计新型抗肿瘤药物。
