Instituto de Química, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, 20550-013, Brazil.
Biometals. 2013 Feb;26(1):151-65. doi: 10.1007/s10534-012-9603-1. Epub 2013 Jan 24.
Complexes [Ga(2Ac4pFPh)(2)]NO(3) (1), [Ga(2Ac4pClPh)(2)]NO(3) (2), [Ga(2Ac4pIPh)(2)]NO(3) (3), [Ga(2Ac4pNO(2)Ph)(2)]NO(3)·3H(2)O (4) and [Ga(2Ac4pT)(2)]NO(3) (5) were obtained with 2-acetylpyridine N(4)-para-fluorophenyl-(H2Ac4pFPh), 2-acetylpyridine N(4)-para-chlorophenyl-(H2Ac4pClPh), 2-acetylpyridine N(4)-para-iodophenyl-(H2Ac4pIPh), 2-acetylpyridine N(4)-para-nitrophenyl-(H2Ac4pNO(2)Ph) and 2-acetylpyridine N(4)-para-tolyl-(H2Ac4pT) thiosemicarbazone. 1-5 presented antimicrobial and cytotoxic properties. Coordination to gallium(III) proved to be an effective strategy for activity improvement against Pseudomonas aeruginosa and Candida albicans. The complexes were highly cytotoxic against malignant glioblastoma and breast cancer cells at nanomolar concentrations. The compounds induced morphological changes characteristic of apoptotic death in tumor cells and showed no toxicity against erythrocytes. 2 partially inhibited tubulin assembly at high concentrations and induced cellular microtubule disorganization, but this does not appear to be the main mechanism of cytotoxic activity.
[Ga(2Ac4pFPh)(2)]NO3（1）、[Ga(2Ac4pClPh)(2)]NO3（2）、[Ga(2Ac4pIPh)(2)]NO3（3）、[Ga(2Ac4pNO2Ph)(2)]NO3·3H2O（4）和[Ga(2Ac4pT)(2)]NO3（5）是通过 2-乙酰吡啶 N(4)-对氟苯基-(H2Ac4pFPh)、2-乙酰吡啶 N(4)-对氯苯基-(H2Ac4pClPh)、2-乙酰吡啶 N(4)-对碘苯基-(H2Ac4pIPh)、2-乙酰吡啶 N(4)-对硝基苯基-(H2Ac4pNO2Ph)和 2-乙酰吡啶 N(4)-对甲苯基-(H2Ac4pT)缩硫代卡巴腙与 Ga(III)配位得到的。1-5 表现出抗菌和细胞毒性特性。证明与镓（III）配位是提高对铜绿假单胞菌和白色念珠菌活性的有效策略。这些配合物在纳摩尔浓度下对恶性神经胶质瘤和乳腺癌细胞具有高度细胞毒性。这些化合物在肿瘤细胞中诱导凋亡死亡的特征形态变化，并且对红细胞没有毒性。2 在高浓度下部分抑制微管组装并诱导细胞微管解聚，但这似乎不是细胞毒性活性的主要机制。
