期刊
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
卷 27, 期 1, 页码 89-109出版社
SPRINGER
DOI: 10.1007/s00775-021-01913-4
关键词
Chromones; Schiff bases; Phenanthrolines; Vanadium; Copper; Anticancer
资金
- Fundacao para a Ciencia e Tecnologia [UIDB/00100/2020, UIDP/00100/2020, UID/Multi/04349/2019]
- FCT [SFRH/BD/108743/2015]
- Koc University School of Medicine (KUSOM)
- Presidency of Turkey
- Fundação para a Ciência e a Tecnologia [SFRH/BD/108743/2015] Funding Source: FCT
New chromone Schiff bases and their Cu(II) complexes were synthesized and characterized, with evaluation of their stability in water and radical scavenging activity. Cu complexes exhibited higher cytotoxicity than the ligands, but lacked selectivity towards cancer cells. The most potent complexes induced cell death through apoptosis pathway.
We report the synthesis, characterization and biological screening of new chromone Schiff bases derived from the condensation of three 6-substituted-3-formyl-chromones with pyridoxal (HL1-3) and its Cu(II) complexes [Cu(L1-3)Cl], 1-3. For the 6-methyl derivative, HL2, the (VO)-O-IV-complex [VO(L-2)Cl] (5), as well as ternary Cu and (VO)-O-IV complexes with 1,10-phenanthroline (phen), [Cu(L-2)(phen)Cl] (4) and [VO(L-2)(phen)Cl] (6), were also prepared and evaluated. Their stability in aqueous medium and radical scavenging activity toward DPPH are screened, with [Cu(L-2)(phen)Cl] (4) showing hydrolytic stability and [VO(L-2)(phen)Cl] (6) high radical scavenging activity. Spectroscopic studies establish bovine serum albumin (BSA), a model for HSA, as a potential reversible carrier of [Cu(L-2)(phen)Cl] in blood with K-BC approximate to 10(5) M-1. The cytotoxic activity of a group of compounds is evaluated against a panel of human cancer cell lines of different origin (ovary, cervix, brain and breast) and compared to normal cells. Our results indicate that Cu complexes are more cytotoxic than the ligands but not selective towards cancer cells. The most potent complexes (4 and 6) are further evaluated for their apoptotic potential, induction of reactive oxygen species (ROS) and genotoxicity. Both complexes efficiently triggered cell death through apoptosis as evaluated by DNA morphology and TUNEL assay, increased ROS formation as determined by DCFDA (2',7'-dichlorodihydrofluorescein diacetate) analysis, and induced genotoxic damage as visualized via COMET assay in all cancer cells under study. Therefore, 4 and 6 may be potential precursor anticancer molecules, yet they need to be targeted toward cancer cells. [GRAPHICS] .
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据