View : 14 Download: 0

Antiplatelet and antithrombotic activities of CP201, a newly synthesized 1,4-naphthoquinone derivative

Title
Antiplatelet and antithrombotic activities of CP201, a newly synthesized 1,4-naphthoquinone derivative
Authors
Jin Y.-R.Hwang K.-A.Cho M.-R.Kim S.-Y.Kim J.-H.Ryu C.-K.Son D.-J.Park Y.-H.Yun Y.-P.
Ewha Authors
유충규
SCOPUS Author ID
유충규scopus
Issue Date
2004
Journal Title
Vascular Pharmacology
ISSN
1537-1891JCR Link
Citation
vol. 41, no. 1, pp. 35 - 41
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
The antiplatelet and antithrombotic activities of a newly synthesized CP201, 2-(3,5-di-tert-butyl-4-hydroxyl)-3-chloro-1,4-naphthoquinone on human platelet aggregation in vitro and murine pulmonary thrombosis in vivo were examined. In addition, the antiplatelet activity of CP201 involved in calcium-signaling cascade was also investigated. CP201 showed concentration-dependent inhibitory effects on platelet aggregation induced by collagen and thrombin, with IC 50 values of 4.1±0.3 and 4.6±0.4 μM, respectively. Orally administered CP201 protected mice against the collagen plus epinephrine-induced thromboembolic death in a dose-dependent manner. On the other hand, CP201 did not alter such coagulation parameters as activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) in human plasma in vitro. These results suggest that the antithrombotic activity of CP201 may be due to antiplatelet rather than anticoagulation activity. CP201 potently inhibited platelet aggregation challenged by calcium ionophore A23187 and thapsigargin, which is a selective inhibitor of the Ca 2+-ATPase pump, in a concentration-dependent manner, indicating that CP201 may have an inhibitory effect on calcium-signaling cascade. This was supported by measuring [Ca 2+] i in platelets loaded with fura-3AM, where CP201 inhibited the rise in cytosolic Ca 2+ mediated by thrombin. Taken together, these results suggest that CP201 may be a promising antithrombotic agent, and the antithrombotic effect of CP201 may be due to antiplatelet activity, which was mediated, at least partly, by the inhibition of cytosolic calcium mobilization. © 2004 Elsevier Inc. All rights reserved.
DOI
10.1016/j.vph.2004.04.001
Appears in Collections:
약학대학 > 약학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE