The influence of the ancillary ligand on the potential of cobalt(<scp>iii</scp>) complexes to act as chaperones for hydroxamic acid-based drugs
作者:Bradley P. Green、Anna K. Renfrew、Alexandra Glenister、Peter Turner、Trevor W. Hambley
DOI:10.1039/c7dt03645k
日期:——
Cobalt(III) chaperones are a promising class of bioreductive prodrugs under investigation for the delivery of cytotoxic ligands to hypoxic solid tumours. Here we investigate a series of cobaltcomplexes as chaperones for hydroxamic acid ligands, comparing the properties of the cyclic cyclen (1,4,7,10-tetraazacyclododecane) ancillary ligand with the tripodal tpa (tris-(2-pyridylmethyl)amine) and tren
钴(III)分子伴侣是一类有前途的生物还原性前药,目前正在研究中,该药物可将细胞毒性配体递送至缺氧性实体瘤。在这里,我们研究了一系列钴配合物作为异羟肟酸配体的分子伴侣,比较了环状三环(1,4,7,10-四氮杂环十二烷)辅助配体与三脚架tpa(三-(2-吡啶基甲基)胺)的性质,以及en(三-(2-氨基乙基)胺)。制备了一个小型的复合物文库,其中包含几种不同的异羟肟酸,包括MMP抑制剂Marimistat和荧光配体C343haH 2,其p K a确定值,还原电位以及在某些情况下的X射线晶体结构。评价了该系列药物对DLD-1结肠癌细胞的抗增殖活性,并通过ICPMS和共聚焦荧光显微镜对荧光C343haH 2复合物的细胞积累进行了监测,发现辅助配体的性质显着影响了复合物的性质,细胞毒性。和细胞分布。
Conformational inversion of 2,2′-bipyridine 1,1′-dioxide chelate ring in a series of (2,2′,2′′-triaminotriethylamine)(4,4′-disubstituted-2,2′-bipyridine 1,1′-dioxide)cobalt(III) complexes
Abstract A new series of cobalt(III) complexes, [Co(2,2′,2′′-triaminotriethylamine)(4,4′-X 2 bpdo)] 3+ (X=Me, MeO, EtO), where 4,4′-X 2 bpdo denotes 4,4′-disubstituted-2,2′-bipyridine1,1′-dioxide, were prepared. The complexes were resolved into a pair of enantiomers (conformational optical isomers), and gradually racemized in water by conformational inversion of the skewed 4,4′-X 2 bpdo chelate ring
Cobalt(III) Chaperone Complexes of Curcumin: Photoreduction, Cellular Accumulation and Light‐Selective Toxicity towards Tumour Cells
作者:Anna K. Renfrew、Nicole S. Bryce、Trevor Hambley
DOI:10.1002/chem.201502702
日期:2015.10.19
wavelength: green light yields free curcumin, whereas blue light induces photolysis of curcumin to a phototoxic product. Confocal fluorescence microscopy and phototocytotoxicity studies in DLD‐1 and MCF‐7 tumourcells demonstrated that the cobalt(III) prodrugs are nontoxic in the dark but accumulate in significant concentrations in the cell membrane. When cells were treated with light for 15 min, the