title: PtI2(DACH), the iodido analogue of oxaliplatin as a candidate for colorectal cancer treatment: chemical and biological features.
abstract: Colorectal cancer (CRC) is a global health problem being the fourth most common cause of death due to cancer worldwide. Oxaliplatin plays a key role in current CRC treatment but shows serious drawbacks, such as a high systemic toxicity and the frequent insurgence of Pt resistance. In search of novel and more efficacious Pt-based drugs for CRC treatment, we synthesized and characterised PtI2(DACH), an oxaliplatin analogue. PtI2(DACH) was obtained through the replacement of bidentate oxalate with two iodides. PtI2(DACH) turned out to be more lipophilic than oxaliplatin, a fact that led to an enhancement of its cellular uptake. In contrast to oxaliplatin, PtI2(DACH) showed a scarce reactivity towards model proteins, while maintaining affinity for a standard DNA oligo. Notably, PtI2(DACH) induced cytotoxicities roughly comparable to those of oxaliplatin in three representative CRC cell lines. Moreover, it was able to trigger cell apoptosis, to an extent even better than cisplatin and oxaliplatin. Overall, a rather promising picture emerges for this novel Pt drug that merits, in our opinion, a deeper and more extensive preclinical evaluation.
authors.affiliation: Laboratory of Metals in Medicine (MetMed), Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy. luigi.messori@unifi.it tiziano.marzo@unifi.it.
authors.forename: D
authors.initials: D
authors.lastname: Cirri
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Viale GB Morgagni 50, 50134 Firenze, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Pillozzi
authors.affiliation: Department of Chemistry and Industrial Chemistry, University of Pisa, via Moruzzi, 13, 56124 Pisa, Italy. tiziano.marzo@dcci.unipi.it.
authors.forename: C
authors.initials: C
authors.lastname: Gabbiani
authors.affiliation: Laboratory of Metals in Medicine (MetMed), Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy. luigi.messori@unifi.it tiziano.marzo@unifi.it.
authors.forename: J
authors.initials: J
authors.lastname: Tricomi
authors.affiliation: Laboratory of Metals in Medicine (MetMed), Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy. luigi.messori@unifi.it tiziano.marzo@unifi.it and Department of Experimental and Clinical Medicine, University of Florence, Viale GB Morgagni 50, 50134 Firenze, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bartoli
authors.affiliation: DIVAL Toscana Srl, Via Madonna del Piano 6, 50119, Sesto Fiorentino, Firenze, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Stefanini
authors.affiliation: Mass Spectrometry Centre (CISM), University of Florence, Via U. Schiff 6, 50019 Sesto Fiorentino, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Michelucci
authors.affiliation: Laboratory of Metals in Medicine (MetMed), Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy. luigi.messori@unifi.it tiziano.marzo@unifi.it.
authors.forename: A
authors.initials: A
authors.lastname: Arcangeli
authors.affiliation: Laboratory of Metals in Medicine (MetMed), Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy. luigi.messori@unifi.it tiziano.marzo@unifi.it.
authors.forename: L
authors.initials: L
authors.lastname: Messori
authors.affiliation: Department of Chemistry and Industrial Chemistry, University of Pisa, via Moruzzi, 13, 56124 Pisa, Italy. tiziano.marzo@dcci.unipi.it and Laboratory of Metals in Medicine (MetMed), Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy. luigi.messori@unifi.it tiziano.marzo@unifi.it.
authors.forename: T
authors.identifier: http://orcid.org/0000-0002-2567-3637
authors.initials: T
authors.lastname: Marzo