Glucal-conjugated sterols as novel vascular leakage blocker: structure-activity relationship focusing on the C17-side chain

Kyeojin Kim; Sony Maharjan; Changjin Lim; Nam-Jung Kim; Vijayendra Agrawal; Young Taek Han; Sujin Lee; Hongchan An; Hwayoung Yun; Hyun-Jung Choi; Young-Guen Kwon; Young-Ger Suh

doi:10.1016/j.ejmech.2014.01.027

Glucal-conjugated sterols as novel vascular leakage blocker: structure-activity relationship focusing on the C17-side chain

Eur J Med Chem. 2014 Mar 21:75:184-94. doi: 10.1016/j.ejmech.2014.01.027. Epub 2014 Jan 25.

Authors

Affiliations

¹ College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
² Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
³ Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
⁴ College of Pharmacy, Woosuk University, Wanju 565-701, Republic of Korea.
⁵ Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea. Electronic address: [email protected].
⁶ College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea. Electronic address: [email protected].

PMID: 24531231
DOI: 10.1016/j.ejmech.2014.01.027

Abstract

A series of glucal-conjugated sterols as novel vascular leakage blocker were identified through design, synthesis and biologically evaluation. In addition, the structure-activity relationship (SAR) of the glucal-conjugated sterols focusing on the C17-side chain was also established. The sterol analogs linked with the rigid C17-side chain side chains exhibited potent cell survival activities. In particular, analog 21l, which possesses a cyclopentyl oxime moiety, was shown to have excellent pharmacological effects on retinal vascular leakage in a diabetic mouse model.

Keywords: Anti-apoptotic agents; Diabetic retinopathy; Ginsenoside Rk1; Oxime; Pregnenolone; Tight junction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects*
Calcium Gluconate / chemical synthesis
Calcium Gluconate / chemistry*
Calcium Gluconate / pharmacology*
Cell Line
Diabetes Mellitus, Experimental / complications
Diabetic Retinopathy / drug therapy*
Diabetic Retinopathy / pathology
Endothelial Cells / drug effects*
Endothelial Cells / pathology
Human Umbilical Vein Endothelial Cells
Mice
Mice, Inbred C57BL
Oximes / chemical synthesis
Oximes / chemistry
Oximes / pharmacology
Permeability / drug effects
Retina / cytology
Retina / drug effects
Retina / pathology
Sterols / chemical synthesis
Sterols / chemistry*
Sterols / pharmacology*
Structure-Activity Relationship

Substances

Oximes
Sterols
Calcium Gluconate