PtI2(DACH), the iodido analogue of oxaliplatin as a candidate for colorectal cancer treatment: chemical and biological features
| Autor: | Luigi Messori, Annarosa Arcangeli, Serena Pillozzi, Elena Michelucci, Damiano Cirri, Matteo Stefanini, Gianluca Bartoli, Tiziano Marzo, Chiara Gabbiani, Jacopo Tricomi |
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| Rok vydání: | 2017 |
| Předmět: |
Drug
Colorectal cancer media_common.quotation_subject colorectal cancer Pharmacology 010402 general chemistry 01 natural sciences Inorganic Chemistry medicine anticancer drugs oxaliplatin analogues protein DNA interaction colorectal cancer neoplasms media_common Cisplatin 010405 organic chemistry Chemistry Cancer oxaliplatin analogues medicine.disease digestive system diseases DNA interaction 0104 chemical sciences Oxaliplatin anticancer drugs Systemic toxicity Apoptosis protein medicine.drug |
| Zdroj: | Dalton Transactions. 46:3311-3317 |
| ISSN: | 1477-9234 1477-9226 |
| DOI: | 10.1039/c6dt03867k |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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