Hasil Pencarian  ::  Simpan CSV :: Kembali

Abstrak :
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.

---

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.

Abstrak :
Salah satu peran industri farmasi adalah untuk mengembangkan agen terapetik yang dapat mencegah, mengurangi, atau menyembuhkan penyakit. Kunci untuk mencapai peran ini adalah melalui penemuan dari senyawa-senyawa baru dapat diandalkan untuk menjadi agen terapetik yang baru. Metode yang saat ini sedang marak dikembangkan adalah pencarian obat dengan menggunakan in silico screening atau dikenal pula dengan nama virtual screening. Salah satu penyakit endemik yang muncul pada abad 20-an adalah AIDS (Acquired Immunodeficiency Syndrome) yang disebabkan oleh Human Immunodeficiency Virus tipe 1 (HIV-1). Virus ini cepat bermutasi sehingga menyebabkan belum adanya obat yang dapat menyembuhkan penyakit ini secara total. Salah satu target enzim yang dapat diinhibisi untuk menghambat replikasi virus adalah protease HIV-1. Pada penelitian kali ini dilakukan virtual screening dengan menggunakan perangkat lunak GOLD untuk mencari kandidat obat inhibitor Protease HIV-1 dengan menggunakan database Tanaman Obat di Indonesia. Virtual screening yang dilakukan adalah structure based virtual screening. Berdasarkan hasil dari virtual screening ini diperoleh 10 kandidat senyawa obat yang diharapkan dapat menjadi obat protease inhibitor. Senyawa tersebut antara lain Quercetin 7,4'-diglucoside, 4-Methylpentyl glucosinolate, Quercetin 3-rutinoside, Glucoraphenin, Glucobrassicin, Luteolin 3'- methylether7-manosyl-(1-2)alloside, Apigenin-7-O(6"-O-p-coumaroylglucoside), Cyanidin 7(3-glucosil-6-malonylglucoside)4'-glucoside, Sinalbin dan 4-Methylsulfinyl butyl glucosinolate dengan kisaran GoldScore dari 86.2803 sampai 95.6252.

---

One role of the pharmaceutical industry is to develop therapeutic agents that can prevent, reduce or cure disease. The key to achieve this role is through the discovery of new compounds that can be counted to be a new therapeutic agent. Recent method being developed is searching a new drug using in silico screening, or also known as virtual screening. One of the endemic disease emerged in the 20th century is AIDS (Acquired Immunodeficiency Syndrome) caused by Human Immunodeficiency Virus type 1 (HIV-1). This virus mutates rapidly causing no drug that can cure this disease completely. One of enzyme target that can be inhibited to block the replication of this virus is HIV-1 protease. Inhibition to the enzyme cause the blocking of protein cleavage in virus maturation process. In this research, virtual screening was performed using GOLD software to find drug candidates as HIV-1 protease inhibitor using the database Tanaman Obat di Indonesia (database of Medicinal Plants in Indonesia). The virtual screening performed was a structure based virtual screening. Based on the results obtained from the virtual screening there were 10 drug candidates which expected to be a protease inhibitor. These compounds were Quercetin 7,4'-diglucoside, 4-Methylpentyl glucosinolate, Quercetin 3-rutinoside, Glucoraphenin, Glucobrassicin, Luteolin 3'-methylether7-manosyl-(1-2)alloside, Apigenin-7-O(6"-O-p-coumaroylglucoside), Cyanidin 7(3-glucosil-6-malonylglucoside)4'-glucoside, Sinalbin dan 4-Methylsulfinyl butyl glucosinolate with GoldScore ranged from 86.2803 to 95.6252.