Biochemistry of Altered Platelet Reactivity in Hypertension

Huzoor-Akbar,

doi:10.1007/978-1-4615-5049-5_20

Cited by 2 publications

(2 citation statements)

References 78 publications

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“…10,11 Platelet aggregation experiments were performed according to a turbidometric method in dual-channel aggregometers interfaced to computers for the acquisition, quantification, presentation, and management of aggregation data. 20 [ 14 C]Serotonin (0.03 µCi/mL) was added to PRP for 20 min prior to the start of the experiment to allow for uptake of label into dense granules. U46619 was used at the minimum concentration required to stimulate maximal aggregation.…”

Section: N-((34-bis(benzyloxy)phenyl)ethyl)(4-nitrophenyl)acetamide (20)mentioning

confidence: 99%

Synthesis and Evaluation of Trimetoquinol Derivatives: Novel Thromboxane A₂/Prostaglandin H₂ Antagonists with Diminished β-Adrenergic Agonist Activity

et al. 1997

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Trimetoquinol (TMQ, 1) is a unique catecholamine with a strong stereodependence for agonism at beta-adrenergic (S > > R) and antagonism at thromboxane A2/prostaglandin H2 (TP; R > > S) receptors. Our laboratory has reported the effects of N-alkylation and modification of the trisubstituted benzyl group in these receptor systems. For iodinated derivative 5, maintaining potency in TP receptor systems (112%) was coupled with maintaining limited potency in beta-adrenergic receptor systems (34% for beta 1 and 47% for beta 2). In this study, several diverse TMQ derivatives were prepared to probe for binding interactions specific to a particular receptor system. Planar amidine 2, which was designed to explore the importance of TMQ's chiral center, showed a dramatic loss of potency (< 1%) in each receptor system. Likewise, the homologation of a previously described N-benzyl derivative (3) to the N-phenylethyl derivative 4 also showed reduced potency (< 3%) in both receptor systems. However, modification of the trimethoxybenzyl group of TMQ to a 4-hydroxy-3-nitrobenzyl group (7) provided a unique lead for TMQ derivatives with significant potency in TP receptor systems (91%) and reduced potency in beta-adrenergic receptor systems (4% for beta 1 and 19% for beta 2).

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Section: N-((34-bis(benzyloxy)phenyl)ethyl)(4-nitrophenyl)acetamide (20)mentioning

confidence: 99%

Synthesis and Evaluation of Trimetoquinol Derivatives: Novel Thromboxane A₂/Prostaglandin H₂ Antagonists with Diminished β-Adrenergic Agonist Activity

et al. 1997

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“…Since the initial discovery of N-Acetyl-S-farnesyl-L-cysteine (AFC) as the first IPC analog to effectively downregulate inflammatory responses in platelets, macrophages, and neutrophils [6][7][8], several different IPC analogs have been discovered and reported to provide a variety of different activities in skin, including inhibiting G-protein coupled receptor…”

Section: Introductionmentioning

confidence: 99%

N-Succinyl-S-Farnesyl-L-Cysteine (SFC): A Novel Isoprenylcysteine Analog with In Vitro Anti-Inflammatory Activity and Clinical Skin Protecting Properties

et al. 2021

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Over the past 15 years, small molecule isoprenylcysteine (IPC) analogs have been identified as a potential new class of topical anti-inflammatories. Clinical studies have demonstrated that IPCs are both safe and effective in promoting healthy skin when applied topically. This work aims to demonstrate N-Succinyl-S-farnesyl-L-cysteine (SFC) as a novel IPC molecule that provides a broad spectrum of benefits for skin. Human promyelocytic cell line HL-60, human dermal microvascular endothelial cells (HDMECs), human dermal fibroblasts (HDFs), and normal human epidermal keratinocytes (NHEKs) were exposed in culture to various inducers to trigger reactive oxygen species, cytokines, or collagenase production. A 49-subject randomized double-blind, vehicle-controlled, split face trial was performed with 1% SFC gel, or 5% niacinamide and vehicle applied for 12 weeks to evaluate anti-wrinkle and anti-aging endpoints. We demonstrated that SFC inhibited GPCR and TLR-induced pro-inflammatory cytokine release in NHEKs and HDMECs from several inflammatory inducers such as UVB, chemicals, cathelicidin, and bacteria. SFC successfully reduced GPCR-induced oxidation in differentiated neutrophils. Moreover, photoaging studies showed that SFC reduced UVA-induced collagenase (pro-MMP-1) production in HDFs. Clinical assessment of 1% SFC gel demonstrated improvement above the vehicle for wrinkle reduction, hydration, texture, and overall appearance of skin. N-Succinyl-S-farnesyl-L-cysteine (SFC) is a novel anti-inflammatory small molecule and is the first farnesyl-cysteine IPC shown to clinically improve appearance and signs of aging, while also having the potential to ameliorate inflammatory skin disorders.

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Biochemistry of Altered Platelet Reactivity in Hypertension

Cited by 2 publications

References 78 publications

Synthesis and Evaluation of Trimetoquinol Derivatives: Novel Thromboxane A₂/Prostaglandin H₂ Antagonists with Diminished β-Adrenergic Agonist Activity

Synthesis and Evaluation of Trimetoquinol Derivatives: Novel Thromboxane A₂/Prostaglandin H₂ Antagonists with Diminished β-Adrenergic Agonist Activity

N-Succinyl-S-Farnesyl-L-Cysteine (SFC): A Novel Isoprenylcysteine Analog with In Vitro Anti-Inflammatory Activity and Clinical Skin Protecting Properties

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Biochemistry of Altered Platelet Reactivity in Hypertension

Cited by 2 publications

References 78 publications

Synthesis and Evaluation of Trimetoquinol Derivatives: Novel Thromboxane A2/Prostaglandin H2 Antagonists with Diminished β-Adrenergic Agonist Activity

Synthesis and Evaluation of Trimetoquinol Derivatives: Novel Thromboxane A2/Prostaglandin H2 Antagonists with Diminished β-Adrenergic Agonist Activity

N-Succinyl-S-Farnesyl-L-Cysteine (SFC): A Novel Isoprenylcysteine Analog with In Vitro Anti-Inflammatory Activity and Clinical Skin Protecting Properties

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Synthesis and Evaluation of Trimetoquinol Derivatives: Novel Thromboxane A₂/Prostaglandin H₂ Antagonists with Diminished β-Adrenergic Agonist Activity

Synthesis and Evaluation of Trimetoquinol Derivatives: Novel Thromboxane A₂/Prostaglandin H₂ Antagonists with Diminished β-Adrenergic Agonist Activity