(2R,4aS,6aS,12bR,14aS,14bR)-N-(2-(2-(2-(2-Azidoethoxy)ethoxy)ethoxy)ethyl)-10-hydroxy-2,4a,6a,9,12b,14a-hexamethyl-11-oxo-1,2,3,4,4a,5,6,6a,11,12b,13,14,14a,14b-tetradecahydropicene-2-carboxamide
Author:
Yuzhu Guo1,
Anyanwu Margrate2ORCID,
Yang Xiao1,
Zimo Ren1,
Gianoncelli Alessandra2ORCID,
Ribaudo Giovanni2ORCID,
Coghi Paolo13ORCID
Affiliation:
1. School of Pharmacy, Macau University of Science and Technology, Macau 999078, China
2. Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
3. State Key Laboratory of Quality Research in Chinese Medicine, Science and Technology Building, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau 999078, China
Abstract
In this report, we discuss the synthesis of a compound obtained from the derivatization of the natural compound celastrol. This derivative is connected to PEG azide moiety through an amide linkage. The linkage was achieved through the activation of the carboxylic acid using HOBt/EDC. The compound was fully characterized by proton (1H), carbon-13 (13C), heteronuclear single quantum coherence (HSQC), correlation spectroscopy (1H-1H-COSY), and distortionless enhancement by polarization transfer (DEPT) NMR. Ultraviolet (UV), Fourier-transform infrared (FTIR), and high-resolution mass spectrometry (HRMS) were also adopted. Computational investigations were conducted to forecast the binding mode between the synthesized compound and sarco-endoplasmic reticulum (SR) Ca2+ transport ATPase (SERCA), a known target for the development of novel therapeutics for rheumatoid arthritis. Additionally, the drug-likeness of the synthesized compound was assessed by predicting its pharmacokinetic properties.
Funder
Macao Science and Technology University
University of Brescia