Joint National Laboratory for Antibody Drug Engineering, School of Basic Medicine Science, Henan University, 475004, Kaifeng, China; State Key Laboratory of Medicinal Chemical Biology, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, China.
Joint National Laboratory for Antibody Drug Engineering, School of Basic Medicine Science, Henan University, 475004, Kaifeng, China.
J Pharm Biomed Anal. 2020 Jun 5;185:113244. doi: 10.1016/j.jpba.2020.113244. Epub 2020 Mar 7.
Currently, controllable linker cleavage at the target site will facilitate the clinical treatment of cancer. Dual-functional prodrugs in combination of carbohydrate as targeting group and pH-sensitive cleavable linker are desired in clinical development. Here, a qualified structure of N-phenylcarbamate-d-gluconhydroximo-1,5-lactam was employed and proved to be a potential candidate prodrug in the drug design. To proof this concept, the possible mechanism of Beckmann rearrangement and the degraded products were confirmed by HPLC and LC-MS under the acid condition mimic lysosome. Hence, the strategy of d-gluconhydroximo-1,5-lactam as a prodrug carrier fabricated with interested drugs will provide a great potential approach for chemotherapy.
目前，在靶位点进行可控连接子断裂将有助于癌症的临床治疗。在临床开发中，同时具有糖作为靶向基团和 pH 敏感可断裂连接子的双功能前药是理想的。在这里，采用了 N-苯甲酰基-d-葡萄糖氢基咪啉-1,5-内酰胺的合格结构，并证明它是药物设计中的潜在候选前药。为了证明这一概念，在模拟溶酶体的酸性条件下，通过 HPLC 和 LC-MS 确认了 Bechmann 重排和降解产物的可能机制。因此，以 d-葡萄糖氢基咪啉-1,5-内酰胺为前药载体与感兴趣的药物结合的策略将为化疗提供一种很有潜力的方法。
