Antiplatelet activity of BRX-018, (6aS,cis)-Malonic acid 3-acetoxy-6a9-bis-(2-methoxycarbonyl-acetoxy)-6,6a,7,11b-tetrahydro-indeno[2,1-c]chromen-10-yl ester methylester

Lee, Gwi-Yeop; Chang, Tong‐Shin; Lee, Ki-Seon; Khil, Lee-Yong; Kim, Deukjoon; Chung, Jin‐Ho; Kim, Young‐Chul; Lee, Byung‐Hoon; Moon, Chang-Hyun; Moon, Chang-Kiu

doi:10.1016/j.thromres.2004.09.018

Cited by 5 publications

(2 citation statements)

References 48 publications

(41 reference statements)

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“…Determination of intracellular free Ca 2R concentration in platelets [Ca 2þ ] i was ascertained by using a fluorescent Ca 2þ indicator Fura-2/AM [13]. Briefly, platelets (4 Â 10 8 platelets/ml) with various doses of agents were incubated with Fura 2/AM (2 mmol/l) for 30 min at 378C, and then stimulated with 1.5 U/ml thrombin for 5 min for evaluation of [Ca 2þ ] i .…”

Section: Determination Of Thromboxane A2mentioning

confidence: 99%

N1-(Quinolin-2-ylmethyl) butane-1, 4-diamine, a polyamine analog

Gao

Ji²

2014

Blood Coagulation &Amp; Fibrinolysis

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The current study intended to examine the signal transduction pathway of N-(quinolin-2-ylmethyl) butane-1, 4-diamine (QMA) in antiplatelet aggregation. Rats were divided randomly into five groups: control group; QMA-treated groups (0.3, 1, and 3 mg/kg); and r-Hirudin-treated group (0.3 mg/kg). Sample groups intravenously injected the corresponding agents once a day for 5 days; control group took 0.9% NaCl in the same way. Ten minutes after the last injection, blood samples were obtained from the rat abdominal aorta. Aggregation ex vivo was tested after irritating platelets by 1.5 U/ml thrombin for 5 min with a platelet aggregometer. Malondialdehyde production, activity of superoxide dismutase and nitric oxide production were determined by the microplate reader. Measurement of [Ca]i was performed using a fluorescence spectrophotometer. Thromboxane A2, cyclic adenosine monophosphate and cyclic guanosine monophosphate levels, vasodilator-stimulated phosphoprotein, and mitogen-activated protein kinase phosphorylation were measured with ELISA kits. Phospholipase C γ2 and protein kinase C were observed by immunoblotting study. QMA inhibited thrombin-induced platelet aggregation ex vivo. QMA significantly elevated superoxide dismutase activity, levels of cyclic adenosine monophosphate, cyclic guanosine monophosphate, nitric oxide, and subsequently promoted vasodilator-stimulated phosphoprotein phosphorylation. Meanwhile, QMA suppressed phospholipase C γ2, protein kinase C and mitogen-activated protein kinase phosphorylation, as well as malondialdehyde, thromboxane A2 formation and [Ca]i mobilization. QMA has a strong antiplatelet potential via its multitarget mechanism.

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Section: Determination Of Thromboxane A2mentioning

confidence: 99%

N1-(Quinolin-2-ylmethyl) butane-1, 4-diamine, a polyamine analog

Gao

Ji²

2014

Blood Coagulation &Amp; Fibrinolysis

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“…(2002) have suggested that another SOCE‐independent mechanism also contributes to Ca 2+ entry in platelets and is activated by DAG. It has been reported that agents with inhibitory effects on the cytosolic Ca 2+ mobilization in platelets may suppress platelet aggregation and thrombus growth (Kang et al ., 2001; Jin et al ., 2004; 2005b; Lee et al ., 2005), whereas few studies have further investigated whether these agents have a differential effect on the Ca 2+ channels involved in modulating intracellular Ca 2+ mobilization in human platelets.…”

Section: Introductionmentioning

confidence: 99%

NP‐313, 2‐acetylamino‐3‐chloro‐1,4‐naphthoquinone, a novel antithrombotic agent with dual inhibition of thromboxane A₂ synthesis and calcium entry

Kuo

Lien

Chang

et al. 2011

British J Pharmacology

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BACKGROUND AND PURPOSE1,4-Naphthoquinones exhibit antiplatelet activity both in vivo and in vitro. In the present study, we investigated the antiplatelet effect of a novel naphthoquinone derivative NP-313, 2-acetylamino-3-chloro-1,4-naphthoquinone and its mechanism of action. EXPERIMENTAL APPROACHWe measured platelet aggregation, Ca 2+ mobilization, thromboxane B2 formation and P-selectin expression and examined several enzymatic activities. Furthermore, we used the irradiated mesenteric venules in fluorescein sodium-treated mice to monitor the antithrombotic effect of NP-313 in vivo. KEY RESULTSNP-313 concentration-dependently inhibited human platelet aggregation induced by collagen, arachidonic acid, thapsigargin, thrombin and A23187. NP-313 also inhibited P-selectin expression, thromboxane B2 formation and [Ca 2+ ]i elevation in platelets stimulated by thrombin and collagen. NP-313 at 10 mM inhibited cyclooxygenase, thromboxane A2 synthase, and protein kinase Ca, whereas it did not affect phospholipase A2 or phospholipase C activity. In the presence of indomethacin and an adenosine 5-diphosphate scavenger, NP-313 concentration-dependently inhibited thrombin-and A23187-induced [Ca 2+ ]i increase through its inhibitory effects on Ca 2+ influx, rather than blocking Ca 2+ release from intracellular stores. NP-313 also inhibited thapsigargin-mediated Ca 2+ influx through store-operated calcium channel but had no effect on Ca 2+ influx through store-independent calcium channel evoked by the diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol. Nevertheless, it had little effect on cyclic AMP and cyclic GMP levels. Also, intravenously administered NP-313 dose-dependently inhibited the thrombus occlusion of the irradiated mesenteric vessels of fluorescein-pretreated mice.

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Biancaea sappan (L.) Tod. Fabaceae

Devanathan¹

2020

Ethnobotany of Mountain Regions

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Antiplatelet activity of BRX-018, (6aS,cis)-Malonic acid 3-acetoxy-6a9-bis-(2-methoxycarbonyl-acetoxy)-6,6a,7,11b-tetrahydro-indeno[2,1-c]chromen-10-yl ester methylester

Cited by 5 publications

References 48 publications

N1-(Quinolin-2-ylmethyl) butane-1, 4-diamine, a polyamine analog

N1-(Quinolin-2-ylmethyl) butane-1, 4-diamine, a polyamine analog

NP‐313, 2‐acetylamino‐3‐chloro‐1,4‐naphthoquinone, a novel antithrombotic agent with dual inhibition of thromboxane A₂ synthesis and calcium entry

Biancaea sappan (L.) Tod. Fabaceae

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Antiplatelet activity of BRX-018, (6aS,cis)-Malonic acid 3-acetoxy-6a9-bis-(2-methoxycarbonyl-acetoxy)-6,6a,7,11b-tetrahydro-indeno[2,1-c]chromen-10-yl ester methylester

Cited by 5 publications

References 48 publications

N1-(Quinolin-2-ylmethyl) butane-1, 4-diamine, a polyamine analog

N1-(Quinolin-2-ylmethyl) butane-1, 4-diamine, a polyamine analog

NP‐313, 2‐acetylamino‐3‐chloro‐1,4‐naphthoquinone, a novel antithrombotic agent with dual inhibition of thromboxane A2 synthesis and calcium entry

Biancaea sappan (L.) Tod. Fabaceae

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NP‐313, 2‐acetylamino‐3‐chloro‐1,4‐naphthoquinone, a novel antithrombotic agent with dual inhibition of thromboxane A₂ synthesis and calcium entry