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 PtI(DACH), an oxaliplatin analogue. PtI(DACH) was obtained through the replacement of bidentate oxalate with two iodides. PtI(DACH) turned out to be more lipophilic than oxaliplatin, a fact that led to an enhancement of its cellular uptake. In contrast to oxaliplatin, PtI(DACH) showed a scarce reactivity towards model proteins, while maintaining affinity for a standard DNA oligo. Notably, PtI(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.

A conformationally constrained mimetic of l-fucose has been employed to explore whether glycan mimicry could be utilized to interfere with the catalytic activity of α-1,3-fucosyltransferases.

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The engineering of the surface of nanomaterials with bioactive molecules allows controlling their biological identity thus accessing to functional materials with tuned physicochemical and biological profiles suited for specific applications....

Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator associated to diverse homeostatic and signaling roles. Enhanced biosynthesis of S1P, mediated by the sphingosine kinase isozymes (SK1 and SK2), is implicated in several pathophysiological conditions and diseases, including skeletal muscle fibrosis, inflammation, multiple sclerosis and cancer. Therefore, therapeutic approaches that control S1P production have focused on the development of SK1/2 inhibitors. In this framework, we designed a series of natural monosaccharide-based compounds to enhance anchoring of the known SK1 inhibitor PF-543 at the polar head of the J-shaped substrate-binding channel. Herein, we describe the structure-based design and synthesis of new glycan-containing PF-543 analogues and we demonstrate their efficiency in a TGFβ1-induced pro-fibrotic assay.