title: Antitumor Activity of Ionic Liquids Based on Ampicillin.
abstract: 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.
authors.affiliation: 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).
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ferraz
authors.affiliation: Laboratório de Farmacologia e Biocompatibilidade Celular, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto (Portugal). jrodrigues@fmd.up.pt.
authors.forename: João
authors.initials: J
authors.lastname: Costa-Rodrigues
authors.affiliation: Laboratório de Farmacologia e Biocompatibilidade Celular, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto (Portugal).
authors.forename: Maria H
authors.initials: MH
authors.lastname: Fernandes
authors.affiliation: Departamento de Química, REQUIMTE-CQFB, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica (Portugal).
authors.forename: Miguel M
authors.initials: MM
authors.lastname: Santos
authors.affiliation: Instituto de Tecnologia Química e Biológica, ITQB, Universidade Nova de Lisboa, Av. da República Estação Agronómica Nacional, 2780-157 Oeiras (Portugal).
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Marrucho
authors.affiliation: Instituto de Tecnologia Química e Biológica, ITQB, Universidade Nova de Lisboa, Av. da República Estação Agronómica Nacional, 2780-157 Oeiras (Portugal).
authors.forename: Luís Paulo N
authors.initials: LP
authors.lastname: Rebelo
authors.affiliation: 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).|Centro de Farmacologia e Biopatologia Química (U38-FCT), Faculdade de Medicina da Universidade do Porto (FMUP) (Portugal).
authors.forename: Cristina
authors.initials: C
authors.lastname: Prudêncio
authors.affiliation: Departamento de Química, REQUIMTE-CQFB, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica (Portugal).
authors.forename: João Paulo
authors.initials: JP
authors.lastname: Noronha
authors.affiliation: Departamento de Química, REQUIMTE-CQFB, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica (Portugal). l.branco@fct.unl.pt.
authors.forename: Željko
authors.initials: Ž
authors.lastname: Petrovski
authors.affiliation: Departamento de Química, REQUIMTE-CQFB, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica (Portugal). z.petrovski@fct.unl.pt.
authors.forename: Luís C
authors.initials: LC
authors.lastname: Branco
mesh_terms: D000667:Ampicillin / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D052578:Ionic Liquids / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D052578:Ionic Liquids; D000667:Ampicillin
keywords: active pharmaceutical ingredients; ampicillin; antitumor agents; ionic liquids; toxicity