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"Penelitian aktivitas penghambatan senyawa 4-[(E)-2-(4-okso-3-fenil-kuinazolin-2-il)etenil]benzensulfonamida terhadap siklooksigenase-2 (COX-2) telah dilakukan untuk menentukan aktivitas senyawa 4-[(E)-2-(4-okso-3-fenil-kuinazolin-2-il)etenil]benzensulfonamida dalam menghambat secara selektif enzim COX-2. Pengujian aktivitas dilakukan menggunakan kit COX (ovine) Inhibitor Screening Assay, dimana prostaglandin (PG) yang dihasilkan ditentukan melalui metode Enzyme Immunoassay (EIA). Selanjutnya diukur menggunakan microplate reader pada λ 415 nm. Persen inhibisi senyawa 4-[(E)-2-(4-okso-3-fenil-kuinazolin-2-il)etenil]benzensulfonamida pada konsentrasi 1, 5, 10, dan 20 μM berturut-turut yaitu 19,50; 33,62; 37,29; dan 42,22. Persen inhibisi senyawa pembanding pertama Aspirin pada konsentrasi 1, 10, 25, dan 50 μM berturut-turut yaitu 3,19; 43,50; 50,56; dan 55,51. Persen inhibisi senyawa pembanding kedua Celecoxib pada konsentrasi 0,01; 0,1; 1; dan 10 μM berturut-turut yaitu 15,99; 38,91; 52,50; dan 81,51. Perbandingan persen inhibisi ketiga senyawa tersebut pada konsentrasi yang sama yaitu 10 μM menunjukkan Celecoxib memiliki aktivitas penghambatan COX-2 tertinggi, sedangkan senyawa uji 4-[(E)-2-(4-okso-3-fenil-kuinazolin-2-il)etenil]benzensulfonamida memiliki aktivitas penghambatan COX-2 terendah dan nilai IC50-nya tidak dapat diperoleh karena dari empat konsentrasi larutan uji yang dianalisis, tidak ada yang menghasilkan persen inhibisi melebihi 50%.

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Research on the inhibitory activity of compound 4-[(E)-2-(4-oxo-3-phenylquinazolin-2-yl)ethenyl]benzensulfonamide on cyclooxygenase-2 (COX-2) was performed to determine the activity of the compound 4-[(E)-2-(4-oxo-3-phenylquinazolin-2-yl)ethenyl]benzensulfonamide in selectively inhibiting COX-2 enzyme.

Activity assays performed using the COX (ovine) Inhibitor Screening Assay kit, in which prostaglandin (PG) that was produced, determined using Enzyme Immunoassay (EIA) method. Next, PG was measured using microplate reader at λ 415 nm. Percent inhibition of compound 4-[(E)-2-(4-oxo-3-phenylquinazolin-2-yl)ethenyl]benzensulfonamide at concentrations of 1, 5, 10, and 20 μM respectively is 19,50; 33,62; 37,29; and 42,22. Percent inhibition of the first comparator compound Aspirin at concentrations of 1, 10, 25, and 50 μM respectively is 3,19; 43,50; 50,56; and 55,51. Percent inhibition of the second comparator compound Celecoxib at concentrations of 0,01; 0,1; 1 and 10 μM respectively is 15,99; 38,91; 52,50; and 81,51.

Comparison of percent inhibition of all three compounds at the same concentration of 10 μM showed that Celecoxib has the highest inhibitory activity on COX-2, while the test compound 4-[(E)-2-(4-oxo-3-phenyl-quinazolin-2-yl)ethenyl]benzensulfonamide have the lowest COX-2 inhibitory activity, and the IC50 value can not be obtained because from the four concentrations of test solutions analyzed, none of which produce over 50% of percent inhibition."

"Siklooksigenase (Cyclooxygenase - COX) merupakan enzim yang mengkonversi asam arakidonat menjadi prostaglandin. Prostaglandin berperan penting dalam menimbulkan respons inflamasi dan berbagai respons fisiologis lainnya. Dikenal dua jenis isozim siklooksigenase, COX-1 dan COX-2. Aktivasi siklooksigenase-2 umumnya terinduksi oleh rangsangan dan tidak terus-menerus sehingga menjadi target inhibisi dari obat-obat selektif inhibitor siklogenase terbaru. Kurkumin, senyawa aktif dari Curcuma longa, dan analog alamiahnya memiliki aktivitas inhibisi sikloksigenase-2 yang teramati secara in vitro dan in vivo pada penelitian sebelumnya. Pada penelitian ini, dilakukan pengujian secara in silico melalui penambatan molekuler untuk mengamati aktivitas inhibisi siklooksigenase-2 beberapa analog kurkumin turunan dibenzilidenasikloheksanon. Dari hasil penambatan molekuler kemudian analog diperingkatkan konstanta inhibisinya, Ki. Analog yang paling poten sebagai inhibitor COX-2 dari hasil penelitian ini adalah analog III. Daerah pengikatan substrat penting untuk COX-2 yang teramati pada penelitan ini meliputi residu-residu Tyr 355, Phe 381, Tyr 385, Leu 384, dan Trp 387.

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Cyclooxygenase (COX) is an enzyme that converting arachidonic acid (AA) to prostaglandin. Prostaglandin has an important role of inducing inflammation and other physiological responses. There are two types of cyclooxygenase isozyme, COX-1 and COX-2. Cyclooxygenase-2 activation in general was induced by stimulation and was not constitutive therefore it became inhibition target of the newer selective cyclooxygenase inhibitor drugs. Curcumin, active compound from Curcuma longa, and its natural analogues were shown to have cyclooxygenase-2 inhibition activity. This activity has been observed by in vitro and in silico method in the previous researches. In this research, in silico test was done using molecular docking method to observe cyclooxygenase inhibition activity of some dibenzilydenecyclohexanone derived curcumin analogues. From the result of molecular docking, the analogues were ranked based on its ΔG binding energy and inhibition constant, Ki. In this research, the most potential analogue as COX-2 inhibitor was analogue III. Important binding area of the COX-2 substrate was comprised of Tyr 355, Phe 381, Tyr 385, Leu 384, and Trp 387 residues."

"Latar belakang: Kolitis ulseratif adalah inflamasi pada kolon yang ditandai dengan peradangan mukosa kolon proksimal hingga rektum. Kolitis ulseratif disebabkan oleh beberapa faktor, yaitu predisposisi genetik, disregulasi sistem imun, alterasi mikrobiota usus, dan faktor lingkungan. Kolitis ulseratif dalam jangka waktu yang lama meningkatkan risiko terjadinya kanker kolorektal sehingga butuh terapi yang efektif. Kolitis ulseratif dapat diobati dengan terapi konvensional berupa pemberian aminosalisilat, steroid, dan agen biologis yang memiliki berbagai efek samping dari ringan hingga cukup parah. Selain itu, pengobatan konvensional ini memiliki interaksi obat, seperti kortikosteroid dengan thiopurin, antifungal, antiviral, dan senyawa lainnya, serta adanya kemungkinan kegagalan terapi. Oleh karena itu, diperlukan penelitian terkait pengobatan alternatif yang efektif dengan efek samping minimal, salah satunya adalah dengan pemanfaatan fitokimia ekstrak kulit delima. Penelitian ini bertujuan untuk membuktikan efek ekstrak kulit delima pada ekspresi COX-2 kolon distal mencit yang diinduksi DSS. Metode: Dua puluh lima mencit Swiss-Webster jantan dibagi menjadi 5 kelompok: normal, kontrol negatif, kontrol positif, terapi ekstrak kulit delima dosis 240 mg/kgBB/hari, dan terapi ekstrak kulit delima dosis 480 mg/kgBB/hari. Setelah diberi perlakuan, mencit dikorbankan dan organ kolon distal diambil untuk membuat preparat jaringan. Preparat kemudian diberikan pewarnaan imunohistokimia dan dilakukan pengukuran ekspresi COX-2 menggunakan ImageJ.Hasil: Pemberian ekstrak etanol kulit delima dosis 240 mg/kgBB mampu menurunkan ekspresi COX-2 secara signifikan (p<0,05) dibandingkan dengan kelompok kontrol negatif. Terlihat adanya penurunan ekspresi COX-2 kolon distal yang diinduksi DSS pada pemberian ekstrak kulit delima dosis 480 mg/kgBB. Simpulan: Ekstrak kulit delima dosis 240 mg/kgBB terbukti dapat menurunkan inflamasi pada kolon distal, melalui penurunan protein COX-2. Terlihat adanya penurunan ekspresi COX-2 dosis 480 mg/kgBB namun tidak signifikan.

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Background: Ulcerative colitis is a condition of inflammation from the proximal colon mucosa to the rectum. Ulcerative colitis is caused by several factors, including genetic predisposition, immune system dysregulation, intestinal microbiota alteration, and environmental factors. Prolong ulcerative colitis increases the risk of developing colorectal cancer, thus an effective treatment is needed. Ulcerative colitis can be treated with conventional therapy such as aminosalicylated, steroids, and biological agents that have mild to severe side effects. Unfortunately, conventional therapy has drug interactions and is possible to failure. Therefore, more research is needed on alternative therapy in order to get an effective treatment with minimum side effects, one of which is the use of pomegranate peel extract. This study aims to prove the effect of pomegranate peel extract in COX-2 expression on DSS-induced mice's distal colon.

Methodes: Twenty five male Swiss-Webster mice were divided into five groups: normal, negative control, positive control, pomegranate peel extract therapy in a dose of 240 mg/kg/day, and pomegranate peel extract therapy in a dose of 480 mg/kg/day. After being treated, the mice were sacrificed and the distal colon organs were taken to make tissue specimens. The tissue speciments were given immunohistochemical staining, which enables us to measure COX-2 expression using ImageJ.

Results: The administration of pomegranate peel ethanol extract at a dose of 240 mg / kgBW significantly reduce COX-2 expression (p <0.05) compared to the negative control group. The administration of pomegranate peel ethanol extract at a dose of 480 mg / kgBW was able to reduce COX-2 expression but it was not significant (p> 0.05) compared to the negative control.

Conclusion: Pomegranate peel extract in a dose of 240 mg/kg/day and 480 mg/kg/day have been shown to reduce inflammation in the distal colon, by reducing the expression of COX-2 protein. The reducing effect of pomegranate peel extract at a dose of 480 mg/kgBW was not significant."

"ABSTRAKSenyawa Etil 4-{4-okso-2-[(E)-2-{4-sulfamoilfeniletenil}-3,4-dihidrokuinazolin-3-il]}benzoat merupakan senyawa baru yang mempunyai kemiripan strukturdengan senyawa diarilheterosiklik, sedangkan sebagian besar inhibitor selektifsiklooksigenase-2 merupakan senyawa diarilheterosiklik, sehingga senyawatersebut diprediksi mempunyai aktivitas menghambat konversi asam arakhidonatmenjadi prostaglandin melalui jalur siklooksigenase. Penelitian ini bertujuanuntuk menguji efek penghambatan siklooksigenase-2 (COX-2) oleh senyawa etil4-{4-okso-2-[(E)-2-{4-sulfamoilfeniletenil}-3,4-dihidrokuinazolin-3-il]}benzoat.Uji aktivitas penghambatan COX-2 dilakukan dengan menggunakan kit COX(ovine) inhibitor screening assay. Prostaglandin yang terbentuk ditentukanmenggunakan metoda Enzyme Immunoassay dan intensitas warna yang dihasilkandiukur serapannya menggunakan plate reader pada panjang gelombang 415 nm.Dari hasil uji didapatkan nilai IC50 senyawa etil 4-{4-okso-2-[(E)-2-{4-sulfamoilfeniletenil}-3,4-dihidrokuinazolin-3-il]}benzoat adalah 16,91 μM.Sebagai pembanding, pengujian juga dilakukan terhadap asetosal dan selekoksib.Hasil yang diperoleh untuk nilai IC50 asetosal dan selekoksib berturut-turut yaitu24,97 μM dan 0,43 μM. Hasil penelitian menunjukkan bahwa senyawa etil 4-{4-okso-2-[(E)-2-{4-sulfamoilfeniletenil}-3,4-dihidrokuinazolin-3-il]}benzoatmempunyai potensi inhibisi lebih kuat dibandingan asetosal tetapi masih lebihrendah dibandingkan selekoksib.

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ABSTRACTEthyl 4-{4-oxo-2-[(E)-2-{4-sulfamoylphenyletenyl}-3,4-dihydroquinazolin-3-

yl]}benzoate compound is a new drug that has structural similarities with diaryl

heterocyclic compound, while some of cyclooxygenase-2 selective inhibitor is a

diaryl heterocyclic compound, so that the compound is predicted to have activity

inhibits the conversion of arachidonic acid into prostaglandins through the

cyclooxygenase. The aim of this study is to the test inhibitory effect of

cyclooxygenase-2 (COX-2) by the ethyl 4-{4-oxo-2-[(E)-2-{4-

sulfamoylphenyletenyl}-3,4-dihydroquinazolin-3-yl]}benzoate compound. Study

of COX-2 inhibitory activity carried out by using a kit COX (ovine) inhibitor

screening assay. Prostaglandins which were formed was determined using the

method of Enzyme Immunoassay and the resulting color intensity was measured

using a plate reader absorbance at a wavelength of 415 nm. From the test results

obtained IC50 value of ethyl 4-{4-oxo-2-[(E)-2-{4-sulfamoylphenyletenyl}-3,4-

dihydroquinazolin-3-yl]}benzoate compound was 16.91 μM. For comparison, the

tests were also done on acetosal and celecoxib. The results obtained for acetosal

and celecoxib IC50 values were 24.97 μM and 0.43 μM, respectively. The results

showed that the ethyl 4-{4-oxo-2-[(E)-2-{4-sulfamoylphenyletenyl}-3,4-

dihydroquinazolin-3-yl]}benzoate compound has stronger inhibitory potency

compared to acetosal but still lower than celecoxib."

"4-[(E)-2-{4-okso-3-(4-metilfenil)-kuinazolin-2-il}vinil]benzensulfonamida merupakan suatu senyawa baru hasil sintesis turunan 4(3H) kuinazolin. Berdasarkan struktur kimianya senyawa ini dapat dimasukkan dalam golongan diarilheterosiklik tersubstitusi gugus sulfonamida. Kebanyakan senyawa golongan tersebut mempunyai aktivitas sebagai inhibisi COX-2. Penelitian ini bertujuan untuk mengetahui besarnya potensi aktivitas senyawa 4-[(E)-2-{4-okso-3-(4-metilfenil)-kuinazolin-2-il}vinil]benzensulfonamida untuk menghambat COX-2. Uji aktivitas dilakukan dengan menggunakan kit enzyme immunoassay dengan selekoksib dan asetosal sebagai pembanding. Hasil penelitian menunjukkan bahwa senyawa ini menunjukkan aktivitas penghambatan terhadap COX-2 dengan IC50 16,94 μM. Potensi aktivitas penghambatan senyawa ini lebih kecil daripada selekoksib (IC50 0,40 μM) namun lebih besar daripada asetosal (IC50 24,07 μM).

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4 - [(E)-2-{4-oxo-3-(4-metylphenyl)-quinazolin-2-yl} vinyl] benzensulfonamide is a new synthetic compound derivative of 4(3H) kuinazolin. Based on the chemical structure of these compounds can be included in the class diarilheterosiklik substituted sulfonamide group. Most of these classes of compounds inhibit COX-2. This study aims to determine the strength of the potential activity of the 4 - [(E) -2 - {4-oxo-3-(4-metylphenyl)-quinazolin-2-yl} vinyl] benzensulfonamide towards inhibition of COX-2. The activity assay was performed using an enzyme immunoassay kit with selekoksib and aspirin as a comparator. The results showed that these compounds owns inhibitory activity towards COX-2 with IC50 16,94 μM. Potential activity inhibition of this compound is smaller than selekoksib (IC50 0,40 μM) but was greater than aspirin (IC50 24,07 μM)."