Novel Low-Toxic Derivative of Celastrol Maintains Protective Effect against Acute Renal Injury

Xun Hu; Mengdi Jia; Yu Fu; Pei Zhang; Zhirong Zhang; Qing Lin

doi:10.1021/acsomega.7b01890

Novel Low-Toxic Derivative of Celastrol Maintains Protective Effect against Acute Renal Injury

ACS Omega. 2018 Mar 31;3(3):2652-2660. doi: 10.1021/acsomega.7b01890. Epub 2018 Mar 6.

Authors

Xun Hu¹, Mengdi Jia¹, Yu Fu¹, Pei Zhang¹, Zhirong Zhang¹, Qing Lin¹

Affiliation

¹ Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Department of Pharmaceutics, West China School of Pharmacy, Sichuan University, No. 17 People's South Road, Chengdu 610041, P. R. China.

Abstract

This study aimed to novelly design and synthesize an amide derivative as a potential substitute of celastrol (CLT). We constituted the compound celastrol-glucosamine (CLG) by conjugating 1-(2-aminoethoxy)-2-glucosamine to celastrol (CLT) and confirmed its chemical structure by ¹H NMR, ¹³C NMR, and LC-MS/MS. Then, the potential efficacy of the CLG was investigated on renal ischemia-reperfusion injury animal models. The results demonstrated that the decorated compound CLG could completely reverse the disease progression as same as CLT. Furthermore, the toxicity of CLG was also fully evaluated in rat blood, liver, kidney, heart, spleen, lung, and reproductive system. Compared to the performance of CLT on normal organs, CLG could remarkably maintain high safety and significantly reduce the side effects. Taken together, the CLG could keep the same efficacy as CLT while processing lower toxicity in vivo.