Ferraz Ricardo, Costa-Rodrigues João, Fernandes Maria H, Santos Miguel M, Marrucho Isabel M, Rebelo Luís Paulo N, Prudêncio Cristina, Noronha João Paulo, Petrovski Željko, Branco Luís C
Departamento de Química, REQUIMTE-CQFB, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica (Portugal).
Ciências Químicas e das Biomoléculas, Escola Superior de Tecnologia da Saúde do Porto do Instituto Politécnico do Porto, Rua Valente Perfeito 322, 4400-330 Vila Nova de Gaia (Portugal).
ChemMedChem. 2015 Sep;10(9):1480-3. doi: 10.1002/cmdc.201500142. Epub 2015 Jul 16.
Significant antiproliferative effects against various tumor cell lines were observed with novel ampicillin salts as ionic liquids. The combination of anionic ampicillin with appropriate ammonium, imidazolium, phosphonium, and pyridinium cations yielded active pharmaceutical ingredient ionic liquids (API-ILs) that show potent antiproliferative activities against five different human cancer cell lines: T47D (breast), PC3 (prostate), HepG2 (liver), MG63 (osteosarcoma), and RKO (colon). Some API-ILs showed IC50 values between 5 and 42 nM, activities that stand in dramatic contrast to the negligible cytotoxic activity level shown by the ampicillin sodium salt. Moreover, very low cytotoxicity against two primary cell lines-skin (SF) and gingival fibroblasts (GF)-indicates that the majority of these API-ILs are nontoxic to normal human cell lines. The most promising combination of antitumor activity and low toxicity toward healthy cells was observed for the 1-hydroxyethyl-3-methylimidazolium-ampicillin pair ([C2 OHMIM][Amp]), making this the most suitable lead API-IL for future studies.
新型氨苄青霉素盐作为离子液体对多种肿瘤细胞系具有显著的抗增殖作用。阴离子型氨苄青霉素与合适的铵、咪唑、鏻和吡啶阳离子组合，产生了活性药物成分离子液体（API-ILs），这些离子液体对五种不同的人类癌细胞系表现出强大的抗增殖活性：T47D（乳腺癌）、PC3（前列腺癌）、HepG2（肝癌）、MG63（骨肉瘤）和RKO（结肠癌）。一些API-ILs的IC50值在5至42 nM之间，这些活性与氨苄青霉素钠盐所显示的可忽略不计的细胞毒性活性水平形成了鲜明对比。此外，对两种原代细胞系——皮肤（SF）和牙龈成纤维细胞（GF）——的细胞毒性非常低，这表明这些API-ILs中的大多数对正常人类细胞系无毒。对于1-羟乙基-3-甲基咪唑鎓-氨苄青霉素对（[C2OHMIM][Amp]），观察到了最有前景的抗肿瘤活性和对健康细胞低毒性的组合，使其成为未来研究中最合适的先导API-IL。
