• 약학회지
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• 제43권6호
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• pp.776-781
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• 1999

Dockings of 4,5-diarylpyrroles into cyclooxygenase-1 and cyclooxygenase-2 were carried out by GOLD program. The sulfonyl groups bonded to 5-phenyl ring of 4,5-diarylpyrroles are directed to Arg513 of COX-2 and Tyr385 of COX-2 docking modes of pyrroles are different from COX-1. Tyr385 and Arg120 of COX-1 and COX-2 have been recognized as important residues. Val523 of COX-2 may be also important. A new COX-2 selective inhibitors could be designed from the docking study.

• 약학회지
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• 제44권3호
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• pp.272-278
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• 2000

The antiinflammatory mechanism of NSAIDs is attributed to the reduction of prostaglandin synthesis by the direct inhibition of cyclooxygenase. Inhibition of prostaglandin production in organs such as stomach and kidney can result in gastric lesions, nephrotoxicity and increased bleeding. In this study, newly designed COX-2 inhibitors, synthesized 1,2-benzothiazine derivatives, were screened in vitro for selectivity of COX-1 and COX-2 inhibition properties. Lead compounds in the structure-activity relationship were studied to synthesize new highly selective COX-2 inhibitors.13 determine inhibitory effect of COX-2, synthesized 1,2-benzothiazine derivatives were screened with accumulation of prostaglandin by lipopolysaccharide (LPS) in aspirin-treated macrophages and murine macropharge cell. Some of synthesized 1,2-benzothiazine derivatives were shown to be effective as selective COX-2 inhibitory activity. Others exhibited a preferential inhibition of COX-2, although some COX-1 inhibitory activity was still present. As a conclusion, simple monomer derivatives were more active than dimer derivatives. Substitution of halogen (Br, C1) on the benzothiazine nucleus slightly enhanced inhibition activity.

• 대한약침학회지
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• 제20권3호
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• pp.207-212
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• 2017

Objectives: Study of the mechanisms involved in cancer progression suggests that cyclooxygenase enzymes play an important role in the induction of inflammation, tumor formation, and metastasis of cancer cells. Thus, cyclooxygenase enzymes could be considered for cancer chemotherapy. Among these enzymes, cyclooxygenase 2 (COX-2) is associated with liver carcinogenesis. Various COX-2 inhibitors cause growth inhibition of human hepatocellular carcinoma cells, but many of them act in the COX-2 independent mechanism. Thus, the introduction of selective COX-2 inhibitors is necessary to achieve a clear result. The present study was aimed to determine the growth-inhibitory effects of new analogues of chalcone epoxide as selective COX-2 inhibitors on the human hepatocellular carcinoma (HepG2) cell line. Methods: Estimation of both cell growth and the amount of prostaglandin E2 (PGE2) production were used to study the effect of selective COX-2 inhibitors on the hepatocellular carcinoma cell. Cell growth determination has done by MTT assay in 24 h, 48 h and 72 h, and PGE2 production has estimated by using ELYSA kit in 48 h and 72 h. Results: The results showed growth inhibition of the HepG2 cell line in a concentration and time-dependent manner, as well as a reduction in the formation of PGE2 as a product of COX-2 activity. Among the compounds those analogues with methoxy and hydrogen group showed more inhibitory effect than others. Conclusion: The current in-vitro study indicates that the observed significant growth-inhibitory effect of chalcone-epoxide analogues on the HepG2 cell line may involve COX-dependent mechanisms and the PGE2 pathway parallel to the effect of celecoxib. It can be said that these analogues might be efficient compounds in chemotherapy of COX-2 dependent carcinoma specially preventing and treatment of hepatocellular carcinomas.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.139-140
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• 2003

Inflammatory as well as oxidative tissue damage has been implicated in pathophysiology of Alzheimer's disease (AD), and non-steroidal anti-inflammatory drugs have been reported to have beneficial effects in the treatment or prevention of AD. In the present study, we investigated the effect of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on inflammatory cell death induced by beta-amyloid, a neurotoxic peptide associated with senile plaques formed in the brains of patients with AD.(omitted)

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2003년도 추계학술대회
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• pp.139-140
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• 2003

• The Korean Journal of Physiology and Pharmacology
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• 제10권1호
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• pp.45-50
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• 2006

Melittin-induced pain model has been known to be very useful for the study of pain mechanism. Melittin-induced nociceptive responses are reported to be modulated by the changes in the activity of excitatory amino acid receptor, calcium channel, spinal serotonin receptor and extracellular signaling-regulated kinase. The present study was undertaken to investigate the role of cyclooxygenase (COX) in the melittin-induced nociception. Changes in mechanical threshold, flinchings and paw thickness were measured before and after intraplantar injection of melittin in the rat hind paw. Also studied were the effects of intraperitonealy administered diclofenac (25 mg & 50 mg/kg), piroxicam (10 mg & 20 mg/kg) and meloxicam (10 mg & 20 mg/kg) on the melittin-induced nociceptions. Intraplantar injection of melittin caused marked reduction of mechanical threshold that was dose-dependently attenuated by non-selective COX inhibitor (diclofenac) and selective COX-1 inhibitor (piroxicam), but not by COX-2 inhibitor (meloxicam). Melittin-induced flinchings were strongly suppressed by non-selective COX and COX-1 inhibitor, but not by COX-2 inhibitor. None of the COX inhibitors had inhibitory effects on melittin-induced increase of paw thickness (edema). These experimental findings suggest that COX-1 plays an important role in the melittin-induced nociceptive responses.

• Journal of Hospice and Palliative Care
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• 제8권1호
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• pp.57-64
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• 2005

Cyclooxygenase-2 (COX-2) selective inhibitors were specifically developed to reduce the risks of gastrointestinal bleeding associated with other NSAID drugs. However, the APPROVe (Adenomatous Polyp Prevention on VIOXX) trials revealed that rofecoxib sometimes exerts prothrombotic effects. Meanwhile, cancer patients, who also carry a risk of thrombosis due to a variety of mechanisms, are often treated with COX-2 selective inhibitors, due to their relative gastrointestinal safety. This report concerns the case of a 46-year old woman with advanced cervical cancer, who had been treated with opioids and a COX-2 selective inhibitor (celecoxib) for 2 months, for the relief of pain associated with her cancer. The patient was admitted due to swelling of the left leg, which was also accompanied by pain. A computerized tomography scan revealed deep vein thrombosis occurring in multiple veins of both legs. After the administration of low-molecular weight heparin and oral warfarin, the patient's symptoms were relieved initially. However, her prothrombin time was found to be prolonged, necessitating the discontinuation of anticoagulation therapy. The patient's dyspnea worsened, ultimately resulting in her death. In conclusion, the administration of cox-2 selective inhibitors should be carefully considered in patients with a number of different risk factors, and assessed on a case-by-case basis.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.114-121
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• 2023

선택적 cyclooxygenase (COX)-2 억제제는 기존의 비스테로이드성 소염제의 위장 부작용을 줄일 수 있는 새로운 대체제이다. 하지만, 최근 혈전을 일으켜 심혈관 질환의 위험을 증가시킨다는 보고가 있다. 따라서 본 연구에서는 유효성분인 ursolic acid를 각각 40, 50%로 극대화한 로즈마리 추출물(RE)의 항염증 효과와 이에 따른 심혈관 부작용의 안전성을 확인하였다. RE의 COX 효소 활성 저해 평가 결과 40, 50% RE는 100 ㎍/mL에서 양성 대조군인 celecoxib 및 rofecoxib와 비슷한 COX-2 저해 활성을 보였고, COX-1 저해 활성은 미미하였다. 이후 Lipopoly-saccharide (LPS)를 조건에 따라 처리한 RAW 264.7 세포에 40, 50% RE 1 ㎍/mL를 처리하여 COX-2, COX-1 유전자 발현, 세포 배양액의 prostaglandin E₂ (PGE₂), thromboxane B₂ (TXB₂) 농도를 확인하였다. 실험 결과 COX-2 유전자 발현은 40% RE가 LPS를 24시간 후처리한 조건에서 감소하였고, 40, 50% RE는 COX-1 유전자 발현 및 PGE₂, TXB₂ 농도에는 유의한 영향을 주지 않는 것으로 확인되었다. 따라서 RE는 혈전 생성에 관여하는 prostaglandins의 균형에 영향을 주지 않아 심혈관 혈전 생성의 위험성이 적을 것으로 사료된다.

• 약학회지
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• 제42권2호
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• pp.214-219
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• 1998

Tissue distributions and association of cyclooxygenase-2 (COX-2) with inflammatory have led us to search for COX-2 selective inhibitors from natural products. Conceptually, COX- 2 selective inhibitors should be expected to retain anti-inflammatory efficacy by inhibition of PGs production while reducing or eliminating the gastric, renal and hemostatic side effects commonly associated with NSAIDs use. Thus, a logical approach to the treatment of inflammatory diseases should involve the inhibitors of COX-2. To develop new COX-2 inhibitors from natural products, two hundred crude drugs were screened by inhibiting PGD2 generation in bone marrow derived mast cells (BMMC). Among them, 6 methanol extracts of crude drugs such as, Bletillae rhizoma, Aconiti kgreani rhizoma, Belamcandae rhizoma, Nelumbinis semen, Gleniae radix, Aurantii immatri pericarpium inhibited more than 85% of BMMC COX-2 activity at a concentration 2.5${\mu}$g/ml.

• 대한정형외과학회지
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• 제55권1호
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• pp.9-28
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• 2020

비스테로이드 소염제(non-steroidal anti-inflammatory drugs, NSAIDs)는 세계적으로 관절염과 같은 만성 통증에 가장 흔히 사용되는 약물이며 성분 및 기전에 따라 다양한 종류가 있다. 장기간 사용 시에는 소화기계 및 심혈관계 합병증 등의 다양한 부작용이 발생할 수 있는 것으로 알려져 있다. 기존의 비선택적 NSAID와 유사한 진통 효과를 지니면서 위장관계 내약성을 보완해줄 수 있는 cyclooxygenase-2 (COX-2) 선택적 NSAID가 많은 기대를 모았으나 2004년 및 2005년도에 심혈관계 안전성에 대한 우려로 rofecoxib과 valdecoxib의 허가가 취하되면서 NSAID 약물의 부작용에 관한 관심은 더욱 증가하고 있다. 따라서 각 약물의 부작용 및 상호작용을 고려하여 필요한 약물을 최소한으로 사용하는 것이 매우 중요하다. 본 논문에서는 NSAID 약물을 복용할 때 발생할 수 있는 부작용 및 각 약물의 특성을 숙지하며 비선택적 NSAID 및 COX-2 선택적 NSAID의 사용과 관련된 최근 연구 및 지침에 대해 알아보고자 한다.