Tamayo Lenka V, Santos Ane F, Ferreira Isabella P, Santos Verlane G, Lopes Miriam T P, Beraldo Heloisa
Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
Departamento de Farmacologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
Biometals. 2017 Jun;30(3):379-392. doi: 10.1007/s10534-017-0013-2. Epub 2017 Apr 13.
Complexes [Ag(HCrPh)]NO·2HO (1) and [Ag(HCrpClPh)]NO (2) were obtained with 3-formyl-6-methylchromone-phenyl hydrazone (HCrPh, HL1) and 3-formyl-6-methylchromone-para-chloro-phenyl hydrazone (HCrpClPh, HL2). Although the hydrazones were inactive, upon coordination to silver(I) antifungal activity significantly improved against several Candida strains. Complexes (1-2) revealed to be more active than silver nitrate, silver sulfadiazine and the reference drug nystatin against Candida parapsilosis. The cytotoxic activities of the hydrazones and their silver(I) complexes were evaluated in comparison with cisplatin on B16F10 (metastatic melanoma) and Melan-a (non-tumorigenic melanocyte) cells. The hydrazones showed low cytotoxicity against B16F10 cells, reducing only about 20% of cell viability at the concentration of 10 μM. Upon coordination to silver(I) the cytotoxic effect did not appreciably change in complex (1) while complex (2) proved to be as cytotoxic as cisplatin and much more cytotoxic than both the free ligand and silver nitrate at 1 μM. Both complexes (1) and (2) were less active than cisplatin on non-malignant Melan-a cells, indicating that these compounds might promote less damage on normal cells.
配合物[Ag(HCrPh)]NO·2HO (1)和[Ag(HCrpClPh)]NO (2)是通过3-甲酰基-6-甲基色酮-苯基腙(HCrPh, HL1)和3-甲酰基-6-甲基色酮-对氯苯基腙(HCrpClPh, HL2)制得的。尽管这些腙没有活性,但与银(I)配位后,对几种念珠菌菌株的抗真菌活性显著提高。配合物(1 - 2)对近平滑念珠菌的活性比硝酸银、磺胺嘧啶银和参比药物制霉菌素更强。将这些腙及其银(I)配合物的细胞毒性活性与顺铂在B16F10(转移性黑色素瘤)和Melan-a(非致瘤性黑素细胞)细胞上进行了比较评估。这些腙对B16F10细胞显示出低细胞毒性,在10 μM浓度下仅使细胞活力降低约20%。与银(I)配位后,配合物(1)的细胞毒性作用没有明显变化,而配合物(2)在1 μM时被证明与顺铂具有相同的细胞毒性,且比游离配体和硝酸银的细胞毒性大得多。配合物(1)和(2)对非恶性Melan-a细胞的活性均低于顺铂,表明这些化合物对正常细胞的损伤可能较小。