title: Three diketopiperazines from marine-derived bacteria inhibit LPS-induced endothelial inflammatory responses.
abstract: Diketopiperazine is a natural products found from bacteria, fungi, marine sponges, gorgonian and red algae. They are cyclic dipeptides possessing relatively simple and rigid structures with chiral nature and various side chains. Endothelial dysfunction is a key pathological feature of many inflammatory diseases, including sepsis. In the present study, three (1-3) of diketopiperazines were isolated from two strains of marine-derived bacteria. The compounds were investigated for their effects against lipopolysaccharide (LPS)-mediated endothelial inflammatory responses in vitro and in vivo. From 1 μM, 1-3 inhibited LPS-induced hyperpermeability, adhesion, and migration of leukocytes across a human endothelial cell monolayer and in mice in a dose-dependent manner suggesting that 1-3 may serve as potential scaffolds for the development of therapeutic agents to treat vascular inflammatory disorders.
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, 80 Dahak-ro, Buk-gu, Daegu 41566, Republic of Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea.
authors.forename: Sae-Kwang
authors.initials: SK
authors.lastname: Ku
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea.
authors.forename: Hyukjae
authors.initials: H
authors.lastname: Choi
authors.affiliation: College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, Kyungpook National University, 80 Dahak-ro, Buk-gu, Daegu 41566, Republic of Korea. Electronic address: baejs@knu.ac.kr.
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D001407:Bacillus / Q000737:chemistry*; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D054659:Diketopiperazines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D001688:Biological Products; D054659:Diketopiperazines; D008070:Lipopolysaccharides
keywords: Diketopiperazine; HUVEC; LPS; Vascular permeability