Photoinduced synthesis and antitumor activity of a phakellistatin 18 analog with an isoindolinone fragment. (4th November 2020)

• Record Type: Journal Article
• Authors: Bao, Yujun; Jiang, Shitian; Zhao, Lishuang; Jin, Yingxue; Yan, Rui; Wang, Zhiqiang
• Is Part Of: New journal of chemistry. Volume 44:Number 44(2020)
• Page Start: 19174
• Page End: 19178
• Publication Date: 2020-11-04
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/d0nj03005h
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : Photoinduced synthesis and antitumor activity of a phakellistatin 18 analog with an isoindolinone fragment. Abstract : Cyclic peptides have become a powerful modality in drug development. Naturally isolated cyclic peptides such as phakellistatins have been found to have broad-spectrum bioactivity. In this paper, we have prepared an analog of phakellistatin 18, and tried to compare its bioactivity with that of our reported phakellistatin 2 analog. It was found that compound 1 derived from phakellistatin 18 showed inferior inhibiting ability compared to the phakellistatin 2 analog, similar to the phenomenon observed in the natural products (phakellistatin 2 presented stronger antitumor activity than that of phakellistatin18). We have performed molecular docking of the two analogs with the MDM2 protein using AutoDock Tools, which showed that the phakellistatin 2 analog presented stronger binding through a H-bond, providing an explanation for the bioactivity difference.