title: Antitumor potential of conjugable valinomycins bearing hydroxyl sites: in vitro studies.
abstract: Following our pioneering studies on the direct and efficient introduction of derivatizable hydroxyl handles into the valinomycin (VLM, 1) structure, a K(+)-ionophore with potent antitumor activity, the ensuing conjugable analogues (HyVLMs 2, 3, and 4) have herein been compared to the parent macrocycle for their potential antiproliferative effects on a panel of cancer cell lines, namely, human MCF-7, A2780, and HepG2, as well as rat C6 cells. On the basis of IC50 values, we find that hydroxyl analogues 3 and 4 are only moderately less active than 1, while analogue 2 experiences a heavily diminished activity. Cytofluorimetric analyses of MCF-7 cells treated with HyVLMs suggest that the latter depolarize mitochondria, thus retaining the typical VLM behavior. It is likely that C6 cells, for which the exceptionally potent cytotoxicity of VLM has never reported previously, follow the same fate, as evidenced by alteration of mitochondrial morphology upon incubation with each ionophore.
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "A. Moro" , via Orabona 4, 70125 Bari, Italy.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Iacobazzi
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Bari "A. Moro" , via Orabona 4, 70126 Bari, Italy ; CNR-Istituto di Chimica dei Composti Organometallici (ICCOM) , Bari Section, via Orabona 4, 70126 Bari, Italy.
authors.forename: Cosimo
authors.initials: C
authors.lastname: Annese
authors.affiliation: Istituto tumori IRCCS ″Giovanni Paolo II″ , viale Flacco 65, 70124 Bari, Italy.
authors.forename: Amalia
authors.initials: A
authors.lastname: Azzariti
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Bari "A. Moro" , via Orabona 4, 70126 Bari, Italy ; CNR-Istituto di Chimica dei Composti Organometallici (ICCOM) , Bari Section, via Orabona 4, 70126 Bari, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: D'Accolti
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "A. Moro" , via Orabona 4, 70125 Bari, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Franco
authors.affiliation: CNR-Istituto di Chimica dei Composti Organometallici (ICCOM) , Bari Section, via Orabona 4, 70126 Bari, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Fusco
authors.affiliation: Dipartimento di Bioscienze, Biotecnologie e Biofarmaceutica, Università degli Studi di Bari "A. Moro" via Orabona 4, 70126 Bari, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: La Piana
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "A. Moro" , via Orabona 4, 70125 Bari, Italy.
authors.forename: Valentino
authors.initials: V
authors.lastname: Laquintana
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "A. Moro" , via Orabona 4, 70125 Bari, Italy.
authors.forename: Nunzio
authors.initials: N
authors.lastname: Denora
keywords: Valinomycin; antitumor activity; cell cycle disturbances; cell death; hydroxylation; targeting