当前位置: X-MOL 学术J. Inorg. Biochem. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Structure-activity relationships for osmium(II) arene phenylazopyridine anticancer complexes functionalised with alkoxy and glycolic substituents.
Journal of Inorganic Biochemistry ( IF 3.9 ) Pub Date : 2020-06-24 , DOI: 10.1016/j.jinorgbio.2020.111154
Russell J Needham 1 , Hannah E Bridgewater 1 , Isolda Romero-Canelón 1 , Abraha Habtemariam 1 , Guy J Clarkson 1 , Peter J Sadler 1
Affiliation  

Twenty-four novel organometallic osmium(II) phenylazopyridine (AZPY) complexes have been synthesised and characterised; [Os(η6-arene)(5-RO-AZPY)X] Y, where arene = p-cym or bip, AZPY is functionalized with an alkoxyl (O-R, R = Me, Et, nPr, iPr, nBu) or glycolic (O-{CH2CH2O}nR*, n = 1–4, R* = H, Me, or Et) substituent on the pyridyl ring para to the azo-bond, X is a monodentate halido ligand (Cl, Br or I), and Y is a counter-anion (PF6, CF3SO3 or IO3). X-ray crystal structures of two complexes confirmed their ‘half-sandwich’ structures. Aqueous solubility depended on X, the AZPY substituents, arene, and Y. Iodido complexes are highly stable in water (X = I ⋙ Br > Cl), and exhibit the highest antiproliferative activity against A2780 (ovarian), MCF-7 (breast), SUNE1 (nasopharyngeal), and OE19 (oesophageal) cancer cells, some attaining nanomolar potency and good cancer-cell selectivity. Their activity and distinctive mechanism of action is discussed in relation to hydrophobicity (RP-HPLC capacity factor and Log Po/w), cellular accumulation, electrochemical reduction (activation of azo bond), cell cycle analysis, apoptosis and induction of reactive oxygen species (ROS). Two complexes show 4× higher activity than cisplatin in the National Cancer Institute (NCI) 60-cell line five-dose screen. The COMPARE algorithm of their datasets reveals a strong correlation with one another, as well as anticancer agents olivomycin, phyllanthoside, bouvardin and gamitrinib, but only a weak correlation with cisplatin, indicative of a different mechanism of action.



中文翻译:

with(II)芳烃苯基偶氮吡啶抗癌复合物的结构活性关系用烷氧基和羟基取代基官能化。

已经合成和表征了二十四种新型有机金属lic(II)苯基偶氮吡啶(AZPY)配合物。[OS(η 6 -arene)(5-RO-的Azpy)X] Y,其中芳烃=  p -cym或BIP,的Azpy与烷氧基官能化(OR,R =甲基,乙基,Ñ PR,PR,Ñ BU)或乙醇酸(O- {CH 2 CH 2 ö} ñ R *,N = 1-4,R * = H,Me中,或Et上的吡啶环)的取代基对位到偶氮键,X是单齿halido配体(Cl,Br或I),和Y为抗衡阴离子(PF 6 -,CF 3 SO 3 -或IO 3 -)。两个配合物的X射线晶体结构证实了它们的“半三明治”结构。水溶性取决于X,AZPY取代基,芳烃和Y。碘配体在水中高度稳定(X = I⋙Br> Cl),并且对A2780(卵巢),MCF-7(乳腺癌)表现出最高的抗增殖活性,SUNE1(鼻咽)和OE19(食道)癌细胞,其中一些获得纳摩尔效价和良好的癌细胞选择性。讨论了它们的活性和独特的作用机理与疏水性的关系(RP-HPLC容量因子和Log P o / w),细胞蓄积,电化学还原(偶氮键激活),细胞周期分析,细胞凋亡和活性氧(ROS)的诱导。在美国国家癌症研究所(NCI)60细胞株五剂量筛选中,两种复合物的活性比顺铂高4倍。他们的数据集的COMPARE算法显示出彼此之间的强相关性,以及抗癌药olivomycin,phyllanthoside,bouvardin和gamitrinib,但与顺铂的相关性很弱,表明存在不同的作用机理。

更新日期:2020-06-24
down
wechat
bug