文献类型：期刊文献

英文题名：Strategy to Regulate the Stability and Reduction Rate of Oxaliplatin-Based Pt(IV) Complexes: Cocrystallization

作者：Zhu, Bin[1,2,3,4,5];Guo, Mei[1,2,3,4,5];Yao, Yi-Chen[1,2,3,4,5];Yao, Yu-Qian[1,2,3,4,5];Hong, Minghuang[1,2,3,4,5];Qi, Ming-Hui[1,2,3,4,5];Ren, Guo-Bin[1,2,3,4,5]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Minist Educ, 130 Meilong Rd, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Me, 130 Meilong Rd, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, 130 Meilong Rd, Shanghai 200237, Peoples R China;[5]East China Univ Sci & Technol, Sch Pharm, Lab Pharmaceut Crystal Engn & Technol, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2023

卷号：23

期号：9

起止页码：6506

外文期刊名：CRYSTAL GROWTH & DESIGN

收录：;EI(收录号：20233614696655);WOS:【SCI-EXPANDED(收录号:WOS:001063214900001)】；

基金：We acknowledgethe support from the National Natural Science Foundation of China (grant nos. 21908055, 22078094), China Postdoctoral Science Foundation (grant no. 2021M701188), Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission), Natural Science Foundationof Shanghai (grant no. 20ZR1413600), and Science and Technology Innovation Program of Suzhou City Social Development (grant no. 2022SS27).

语种：英文

外文关键词：Benzoic acid - Oxalic acid - Platinum compounds - Single crystals - Synthesis (chemical) - Thermoanalysis - X ray diffraction

摘要：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.