title: Water-soluble derivatives of 4-oxo-N-(4-hydroxyphenyl) retinamide: synthesis and biological activity.
abstract: A novel series of 4-oxo-N-(4-hydroxyphenyl) retinamide (4-oxo-4-HPR) derivatives were synthesized with the aim of increasing the poor solubility of the parent compound in biological fluids, while maintaining the cytotoxic activity and the dual mechanism of action. The most promising compound 13a showed antiproliferative/apoptotic activity. The analysis of its mechanism of action revealed that it retained the particular characteristic of 4-oxo-4-HPR which is able to induce cell cycle arrest during the mitotic phase, coupled with the formation of aberrant mitotic spindles.
authors.affiliation: Department of Food, Environmental and Nutritional Sciences, Division of Chemistry and Molecular Biology, Università degli Studi di Milano, Milano, Italy. loana.musso@unimi.it.
authors.forename: Loana
authors.initials: L
authors.lastname: Musso
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Tiberio
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Appierto
authors.affiliation: Department of Food, Environmental and Nutritional Sciences, Division of Chemistry and Molecular Biology, Università degli Studi di Milano, Milano, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Cincinelli
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Cavadini
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Cleris
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Daidone
authors.affiliation: Department of Food, Environmental and Nutritional Sciences, Division of Chemistry and Molecular Biology, Università degli Studi di Milano, Milano, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Dallavalle
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D017313:Fenretinide / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: C494898:4-oxofenretinide; D014867:Water; D017313:Fenretinide
keywords: 4-oxo-4-HPR; antimitotic activity; antiproliferative activity; fenretinide; water-soluble drugs