Vascular barrier protective effects of 3-N- or 3-O-cinnamoyl carbazole derivatives.
In this Letter, we investigated the barrier protective effects of 3-N-(MeO)n-cinnamoyl carbazoles (BS 1; n=1, BS 2; n=2, BS 3; n=3) and 3-O-(MeO)3-cinnamoyl carbazole (BS 4) against high-mobility group box 1 (HMGB1)-mediated vascular disruptive responses in human umbilical vein endothelial cells (HUVECs) and in mice for the first time. Data showed that BS 2, BS 3, and BS 4, but not BS 1, inhibited HMGB1-mediated vascular disruptive responses and transendothelial migration of human neutrophils to HUVECs. BS 2, BS3, and BS 4 also suppressed HMGB1-induced hyperpermeability and leukocyte migration in mice. Interestingly, the barrier protective effects of BS 3 and BS 4 were better than those of BS 2. These results suggest that the number of methoxy groups substituted on the cinnamamide or cinnamate moiety of the 9H-3-carbazole derivative is an important pharmacophore for the barrier protective effects of these compounds.
Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 712-715, Republic of Korea.
Sae-Kwang
SK
Ku
College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejon 305-764, Republic of Korea.
Jee-Hyun
JH
Lee
College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejon 305-764, Republic of Korea.
Yuseok
Y
O
College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 702-701, Republic of Korea; Department of Biochemistry and Cell Biology, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 702-422, Republic of Korea.
Wonhwa
W
Lee
College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejon 305-764, Republic of Korea. Electronic address: gysong@cnu.ac.kr.
Gyu-Yong
GY
Song
College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 702-701, Republic of Korea. Electronic address: baejs@knu.ac.kr.
Jong-Sup
JS
Bae
D000818:Animals; D002227:Carbazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D024243:HMGB1 Protein / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D010539:Permeability / Q000187:drug effects; D013329:Structure-Activity Relationship
D002227:Carbazoles; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C582808:HMGB1 protein, mouse
3-N-Cinnamoyl carbazole; 3-O-Cinnamoyl carbazole; HMGB1; Vascular barrier integrity