Characterization of chemical profiles of pH-sensitive cleavable D-gluconhydroximo-1, 5-lactam hydrolysates by LC-MS: A potential agent for promoting tumor-targeted drug delivery

Abstract

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.

Keywords: Beckmann rearrangement; N-phenylcarbamate-d-gluconhydroximo-1,5-lactam; Prodrug; pH sensitive.