Journal
CRYSTAL GROWTH & DESIGN
Volume 23, Issue 9, Pages 6506-6516Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.cgd.3c00480
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In order to overcome the limitations of oxaliplatin (OXA), such as side effects and toxicity, attention has been given to the use of OXA-based Pt-(IV) complexes as oral prodrugs. This study focused on the preparation and characterization of six cocrystals of trans-[Pt-(R,R-DACH)-(oxalate)-(OH)(2)] (DHOXA) to investigate their stability and reduction rate. The results showed that DHOXA-HYD dihydrate (DHOXA-HYD-DH) significantly improved stability and the reduction rate, and also increased cytotoxicity and safety in cancer cells. This study provides a new method for developing OXA-based Pt-(IV) complexes as prodrugs.
To overcome the clinical limitations of oxaliplatin (OXA), such as side effects and toxicity, increasing attention was paid to the use of OXA-based Pt-(IV) complexes as oral administration prodrugs. In this study, we prepared trans-[Pt-(R,R-DACH)-(oxalate)-(OH)(2)] (DHOXA) as a model of OXA-based Pt-(IV) complexes and synthesized six cocrystals of DHOXA to investigate their stability in pH 1.2 and 7.4 buffer and the reduction rate of producing OXA. Six cocrystals of DHOXA with oxalic acid, hydroquinone (HYD), benzoic acid, salicylic acid, 3,5-difluorobenzoic acid, and 3-hydroxy-2-naphthoic acid were characterized by single-crystal X-ray diffraction, powder X-ray diffraction, and thermal analysis. Further contrastive analysis of the dissolution behavior and reduction test of the six cocrystals of DHOXA showed that DHOXA-HYD dihydrate (DHOXA-HYD-DH) significantly improved the performances of the stability in hydrochloric acid (pH 1.2) and the reduction rate. Besides, the cytotoxicity studies showed that DHOXA-HYD-DH increased cytotoxicity to cancer cells and possessed higher safety. The study provides a new method to develop the OXA-based Pt-(IV) complexes as prodrugs.
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