Departamento de Química Inorgánica, Facultad de Ciencias, Instituto de Síntesis Química y Catálisis Homogénea , Universidad de Zaragoza-CSIC , Pedro Cerbuna 12 , 50009 Zaragoza , Spain.
Departamento de Biología Molecular e Ingeniería Bioquímica, Área de Toxicología , Universidad Pablo de Olavide , Ctra. Utrera, Km 1 , 41013 Sevilla , Spain.
Inorg Chem. 2020 Feb 17;59(4):2464-2483. doi: 10.1021/acs.inorgchem.9b03334. Epub 2020 Jan 27.
The reactivity of the multisite (amino)cyclotriphosphazene ligands, [NP(NHCy)] and [NP(NHCy)(NMe)], has been explored in order to obtain silver(I) metallophosphazene complexes. Two series of cationic silver(I) metallophosphazenes were obtained and characterized: NP(NHCy){AgL} [ = 2, L = PPh (), PPhMe (); = 3, L = PPh (), PPhMe (), TPA (TPA = 1,3,5-triaza-7-phosphaadamantane, )] and --NP(NHCy)(NMe){AgL} [ = 2, L = PPh (), PPhMe (); = 3, L = PPh (), PPhMe ()]. , , and have also been characterized by single-crystal X-ray diffraction, thereby allowing key bonding information to be obtained. Compounds -, , and were screened for in vitro cytotoxic activity against two tumor human cell lines, MCF7 (breast adenocarcinoma) and HepG2 (hepatocellular carcinoma), and for antimicrobial activity against five bacterial species including Gram-positive, Gram-negative, and Mycobacteria strains. Both the IC and MIC values revealed excellent biological activity for these metal complexes, compared with their precursors and cisplatin and also AgNO and silver sulfadiazine, respectively. Both IC and MIC values are among the lowest values found for any silver derivatives against the cell lines and bacterial strains used in this work. The structure-activity relationships were clear. The most cytotoxic and antimicrobial derivatives were those with the triphenylphosphane and [NP(NHCy)] ligands. A significant improvement in the activity was also observed upon a rise in the number of silver atoms linked to the phosphazene ring.
为了获得银（I）金属膦氮杂环三磷杂环戊烯配合物，研究了多（氨基）环三磷杂环戊烯配体[NP（NHCy）]和[NP（NHCy）（NMe）]的反应性。获得并表征了两个系列的阳离子银（I）金属膦氮杂环三磷杂环戊烯：[NP（NHCy）{AgL}]（TfO）[ = 2，L = PPh（），PPhMe（）； = 3，L = PPh（），PPhMe（），TPA（TPA = 1,3,5-三氮杂-7-磷杂金刚烷，）]和-[NP（NHCy）（NMe）{AgL}]（TfO）[ = 2，L = PPh（），PPhMe（）； = 3，L = PPh（），PPhMe（）]。 ， ，和 也通过单晶 X 射线衍射进行了表征，从而获得了关键的键合信息。化合物 - ， ，和 针对两种肿瘤人类细胞系 MCF7（乳腺癌）和 HepG2（肝癌）进行了体外细胞毒性活性筛选，并针对包括革兰氏阳性，革兰氏阴性和分枝杆菌菌株在内的五种细菌进行了抗菌活性筛选。与它们的前体物以及顺铂和 AgNO 和磺胺嘧啶银相比，这些金属配合物的 IC 和 MIC 值均表现出优异的生物活性。无论是 IC 还是 MIC 值，均为针对该工作中使用的细胞系和细菌菌株的任何银衍生物中最低值之一。结构-活性关系很明显。具有三苯基膦和[NP（NHCy）]配体的最具细胞毒性和抗菌性的衍生物。还观察到随着与膦氮杂环三磷杂环戊烯环相连的银原子数量的增加，活性也得到了显著提高。
