• Journal of Integrative Natural Science
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• v.5 no.1
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• pp.22-26
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• 2012

Chemokine receptor antagonists have potential applications in field of drug discovery. Although the chemokine receptors are G-protein-coupled receptors, their cognate ligands are small proteins (8 to 12 kDa), and so inhibiting the ligand/receptor interaction has been challenging. In particular, CCR2 and CCR5 and their ligands have been implicated in the pathophysiology of a number of diseases, including rheumatoid arthritis and multiple sclerosis. Based on their roles in disease, they have been attractive targets for the pharmaceutical industry, targeting both CCR2 and CCR5 could be a useful strategy. Because of the importance of these receptors, providing information regarding the binding site is of prime importance. Herein, we report the comparison of CCR2 of CCR5 binding sites both sequentially as well as structurally. We also urged the importance of crucial residues in the binding site, to facilitate the development of dual antagonists targeting both the receptors. These results could also be useful for the design of novel and potent dual CCR2 and CCR5 antagonists using structure based drug design.

• The Korean Journal of Pain
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• v.35 no.2
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• pp.173-182
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• 2022

Background: Neurokinin-1 (NK1) and calcitonin gene-related peptide (CGRP) play a vital role in pain pathogenesis, and these proteins' antagonists have attracted attention as promising pharmaceutical candidates. The authors investigated the anti-nociceptive effect of co-administration of the CGRP antagonist and an NK1 antagonist on pain models compared to conventional single regimens. Methods: C57Bl/6J mice underwent sciatic nerve ligation for the neuropathic pain model and were injected with 4% formalin into the hind paw for the inflammatory pain model. Each model was divided into four groups: vehicle, NK1 antagonist, CGRP antagonist, and combination treatment groups. The NK1 antagonist aprepitant (BIBN4096, 1 mg/kg) or the CGRP antagonist olcegepant (MK-0869, 10 mg/kg) was injected intraperitoneally. Mechanical allodynia, thermal hypersensitivity, and anxiety-related behaviors were assessed using the von Frey, hot plate, and elevated plus-maze tests. The flinching and licking responses were also evaluated after formalin injection. Results: Co-administration of aprepitant and olcegepant more significantly alleviated pain behaviors than administration of single agents or vehicle, increasing the mechanical threshold and improving the response latency. Anxiety-related behaviors were also markedly improved after dual treatment compared with either naive mice or the neuropathic pain model in the dual treatment group. Flinching frequency and licking response after formalin injection decreased significantly in the dual treatment group. Isobolographic analysis showed a meaningful additive effect between the two compounds. Conclusions: A combination pharmacological therapy comprised of multiple neuropeptide antagonists could be a more effective therapeutic strategy for alleviating neuropathic or inflammatory pain.

• Journal of Integrative Natural Science
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• v.5 no.2
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• pp.65-71
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• 2012

Neuropeptide Y (NPY), a 36-amino acid polypeptide, is a member of the pancreatic polypeptide family, which consists of NPY, peptide YY (PYY) and pancreatic polypeptide (PP). The neuropeptide Y (NPY) receptors called Y receptors belongs to G-protein coupled that are involved in a variety of physiological functions such as appetite regulation, circadian rhythm and anxiety. Five receptor subtypes have been cloned in mammals (Y1, Y2, Y4, Y5, and Y6) of which four are functional. In this short review, information about the functional NYP receptors was analyzed. Sequence analyses were done between these receptors to identify the relationships between them. Phylogram was generated between these receptors to identify the close homologue between these receptors. Our sequence analyses found that Y1 and Y4 receptors are close than the other receptors. Further structure based analysis could be useful to identify subtype selective antagonists and dual antagonists targeting Y1 and Y4 receptors.

• Bulletin of the Korean Chemical Society
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• v.29 no.1
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• pp.111-116
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• 2008

A piperazinylalkylisoxazole library containing 86 compounds was constructed and evaluated for the binding affinities to dopamine (D3) and serotonin (5-HT2A/2C) receptor to develop antipsychotics. Dopamine antagonists (DA) showing selectivity for D3 receptor over the D2 receptor, serotonin antagonists (SA), and serotonin-dopamine dual antagonists (SDA) were identified based on their binding affinity and selectivity. The analogues were divided into three groups of 7 DAs (D3), 33 SAs (5-HT2A/2C), and 46 SDAs (D3 and 5-HT2A/2C). A classification model was generated for identifying structural characteristics of those antagonists with different affinity profiles. On the basis of the results from our previous study, we conducted the generation of the decision trees by the recursive-partitioning (RP) method using Cerius2 2D descriptors, and identified and interpreted the descriptors that discriminate in-house antipsychotic compounds.

• The Korean Journal of Mycology
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• v.19 no.3
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• pp.231-237
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• 1991

This study was conducted in order to find out biological control of sesame wilt and blight caused by Fusarium of oxysporum f. sp. vasinfectum and Phytophthora nicotianae var. parasitica by using Streptomyces spp. Two sesame pathogens, Fusarium oxysporum f. sp. vasinfectum and Phytophthora nicotianae var. parasitica were purely isolated from diseased sesame plants of the field. Streptomyces species were isolated from 72 soil samples collected from red pepper and sesame uplands in Chungbuk and selected as antagonists according to the results of dual culture. The selected Streptomyces isolates such as St-11 and St-20 were confirmed their antagonistic effect through mycelial inhibition zone and inhibitory effects on the mycelial growth of the pathogens by culture filterate of the antagonists. Inhibitory effects on the conidial germination of Fusarium oxysporum vasinfectum and Phytophthora nicotianae parasitica by the antagonists were also tested in addition to mycelial Iysis. The antagonists St-11 and St-20 showed inhibitory effect on growth of sesame seedlings after seeds soaked in the suspension. Effect of soil inoculation with antagonist St-11 showed 40 to 78 percent of control effect for two diseases in comparison with control under greenhouse.

• International Journal of Industrial Entomology and Biomaterials
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• v.20 no.1
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• pp.1-5
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• 2010

The studies have been conducted to control the soil borne fungal pathogens viz, Fusarium solani (Mart) Sacc. and Alternaria tenuissima the incitants of root rot and die-back diseases on mulberry stem cuttings planted in the mulberry nurseries and also in established mulberry gardens ten plant extracts with 10% concentration except Lantana camara (undiluted) were tested through poisoned food technique and four biofungicides were also screened by dual culture method under in vitro conditions. Plant extract of Prosopis juliflora showed the maximum inhibition on the mycelial growth (81.2% over A. tenuissima and 80.0% over F. solani) and followed by L. camara (66.7% over A. tenuissima and 68.9% over F. solani). Among the antagonists Pseudomonas fluorescens and Trichoderma viride showed maximum inhibition on the mycelial growth of both pathogenic fungi. The promising plant extracts (P. juliflora and L. camara) and antagonists (P. fluorescens and T. viride) were tested against both the pathogenic fungi under in vivo conditions along with the existing popular chemical Mancozeb. All the tested plant products and bio-fungicides showed inhibitory effect on both fungi. But the maximum survival percentage of mulberry cuttings was recorded in the treatment with T. viride (95% against F. solani and 90% against A. tenuisssima) followed by P. fluorescens (90% against both fungi) and T. harzianum (80% against F. solani and 85% against A. tenuisssima). Incase of the treatments with plant extracts and chemical fungicide the P. juliflora (60% against F. solani and 55% against A. tenuisssima) showed higher survival percentage and followed by L. camara (55% against F. solani and 50% against A. tenuisssima) and Mancozeb (55% against both fungi). In case of control only 10% of survival was recorded in F. solani inoculated cuttings and 15% survival in A. tenuissima inoculated cuttings.

• Korean Journal of Clinical Pharmacy
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• v.34 no.2
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• pp.79-99
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• 2024

Background: There was an important revision of the Korean Clinical Practice Guideline for Stroke (KCPGS) for antithrombotic therapy in patients with acute ischemic stroke in 2022. This review is to provide an updated information in this revision. Methods: The revision history by year after the first announcement was examined for each topic, focusing on antithrombotic therapy during acute phase which was revised in 2022. We compared before and after the revision, and investigated the clinical outcomes presented as evidence. It was also compared with the current U.S. guidelines. Results: The major changes about antiplatelet therapy are a clause stating that dual antiplatelet therapy with clopidogrel and aspirin initiated within 24 hours from the stroke onset and maintained for up to 21-30 days is recommended as an acute treatment, as well as the clause that antithrombotic therapy may be initiated within 24 hours after intravenous thrombolytics and that the use of glycoprotein IIb/IIIa receptor antagonists can be considered in highly selected patients as rescue therapy taking into account of benefit and risk. The change to the use of anticoagulants is that it may be reasonable to start oral anticoagulant between 4 and 14 days after stroke onset for patients with acute ischemic stroke and atrial fibrillation. Conclusions: It will be helpful in improving health outcomes for clinical pharmacists to be aware of the latest information for antithrombotic therapy and to actively use it in pharmaceutical care of stroke patients.

• Journal of Integrative Natural Science
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• v.5 no.1
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• pp.18-21
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• 2012

The resistance of tumour cells against cytotoxic drug is significant limitation in successful chemotherapeutic treatment of cancer. To date, no crystal structure is available for human P-gp. We developed homology model for human P-gp NBD2 by using coordinates of transporter associated protein (TAP1). Docking study was performed for 8-geranyl-chrysin (Flavonoids) inhibitor in the NBD2 model. Ligand-protein interactions were determined which indicates that the 8-geranyl chrysin shares two overlapping sites in the cytosolic domains of P-gp, the ATP site and a hydrophobic steroid-binding site.

• Proceedings of the Korean Society of Plant Pathology Conference
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• 2003.10a
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• pp.93.2-94
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• 2003

In our previous studies, we selected three antagonistic bacteria, KJ1R5, KJ2C12, and KJ9C8 against Phytophthora capsici, the casual agent of Phytophthora blight of pepper. For elucidating production, root colonization, and total microbial activity were investigated. The dual culture assay was accomplished to elucidate existence of antibiotics. In this assay, any antagonistic bacteria did not inhibit growth of six important fungal plant pathogens, suggesting that these antagonists do not produce antibiotics. root surface or rhizosphere soil colonizations were examined with spontaneous rifampicin-resistant mutants equal to antagonistic ability of wild types. KJ2C12 colonized consistently rhizosphere soil while yellowish colonies of KJ1R5 and KJ9C8 well colonized root surfaces and rhizosphere soil. Total microbial activity in pots treated with the antagonistic bacteria was measured using fluorescein diacetate hydrolysis. total microbial activity of three antagonistic bacteria treatments was significantly higher than that of buffer-treated control until 4days after treatment. However, total microbial activity of treatment of three antagonistic bacteria decreased after 7 days. These results indicate that the antagonistic bacteria, KJ1R5 and KJ9C8 colonized and protected roots well against Phytophthora blight of pepper through competition of infection courts, especially competitions.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.6
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• pp.675-686
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• 2017

Orthostatic hypotension (OH) is associated with symptoms including headache, dizziness, and syncope. The incidence of OH increases with age. Attenuation of the vestibulosympathetic reflex (VSR) is also associated with an increased incidence of OH. In order to understand the pathophysiology of OH, we investigated the physiological characteristics of the VSR in the disorder. We applied sodium nitroprusside (SNP) to conscious rats with sinoaortic denervation in order to induce hypotension. Expression of pERK in the intermediolateral cell column (IMC) of the T4~7 thoracic spinal regions, blood epinephrine levels, and blood pressure were evaluated following the administration of glutamate and/or SNP. SNP-induced hypotension led to increased pERK expression in the medial vestibular nucleus (MVN), rostral ventrolateral medullary nucleus (RVLM) and the IMC, as well as increased blood epinephrine levels. We co-administered either a glutamate receptor agonist or a glutamate receptor antagonist to the MVN or the RVLM. The administration of the glutamate receptor agonists, AMPA or NMDA, to the MVN or RVLM led to elevated blood pressure, increased pERK expression in the IMC, and increased blood epinephrine levels. Administration of the glutamate receptor antagonists, CNQX or MK801, to the MVN or RVLM attenuated the increased pERK expression and blood epinephrine levels caused by SNP-induced hypotension. These results suggest that two components of the pathway which maintains blood pressure are involved in the VSR induced by SNP. These are the neurogenic control of blood pressure via the RVLM and the humoral control of blood pressure via epinephrine release from the adrenal medulla.