Co(II) complexes having a ferrocene-based curcuminoid (Fc-curH) ligand viz. [Co(L)₂(Fc-cur)]ClO₄ (1, 2), where L is phenanthroline base, namely, 1,10-phenanthroline (phen in 1) and dipyrido[3,2-a:2’,3’-c]phenazine (dppz in 2) have been synthesized, characterized and evaluated as photochemotherapeutic agents in vitro. The corresponding Co(II) complexes of the naturally occurring polyphenol curcumin (curH), namely, [Co(L)₂(cur)]ClO₄ (3, 4), where L is phen (in 3) and dppz (in 4) were synthesized and their photo-induced anticancer activities compared with their ferrocene containing counterparts 1 and 2. The Co(II) acetylacetonato complex viz. [Co(phen)₂(acac)]ClO₄ (5) was structurally characterized through X-ray crystallography and used as control for cellular experiments. The Co(II) complexes having ferrocene-based curcuminoid are remarkably stable at physiological condition with higher lipophilicity compared to their curcumin analogues. The complexes display significant binding propensity to calf thymus (ct) DNA and human serum albumin (HSA). The complexes 1–4 display remarkable visible light induced cytotoxicity with the ferrocenyl analogues showing more phototoxic index (PI). The Co(II) curcumin complexes localize in the nucleus and mitochondria of A549 cells. The primary cell death mechanism is believed to be apoptotic in nature induced by light assisted generation of reactive oxygen species (ROS).

Graphic abstract

具有基于二茂铁的类姜黄素 (Fc-curH) 配体的 Co(II) 配合物，即. [Co(L) ₂ (Fc-cur)]ClO ₄ ( 1 , 2 )，其中L是菲咯啉碱基，即1,10-菲咯啉(phen in 1 )和联吡啶并[3,2-a:2'， 3'-c]吩嗪 (dppz in 2 ) 已被合成、表征和评估为体外光化学治疗剂。天然存在的多酚姜黄素 (curH) 的相应 Co(II) 配合物，即 [Co(L) ₂ (cur)]ClO ₄ ( 3 , 4 )，其中 L 是 phen (in 3 ) 和 dppz (in 4) 被合成，并将它们的光诱导抗癌活性与含有二茂铁的对应物1和2进行比较。Co(II) 乙酰丙酮络合物即. [Co(phen) ₂ (acac)]ClO ₄ ( 5 ) 通过 X 射线晶体学进行结构表征，并用作细胞实验的对照。具有二茂铁类姜黄素的 Co(II) 配合物在生理条件下非常稳定，与姜黄素类似物相比具有更高的亲脂性。该复合物显示出对小牛胸腺 (ct) DNA 和人血清白蛋白 (HSA) 的显着结合倾向。配合物1 – 4显示出显着的可见光诱导的细胞毒性，而二茂铁基类似物显示出更高的光毒性指数 (PI)。Co(II) 姜黄素复合物位于 A549 细胞的细胞核和线粒体中。原发性细胞死亡机制被认为是由光辅助产生活性氧 (ROS) 诱导的细胞凋亡。

图形摘要