Kanker leukemia merupakan suatu penyakit keganasan pada sistem hematopoiesis yang ditandai dengan akumulasi leukosit ganas di sumsum tulang dan darah tepi. Reseptor CK2-α (Casein Kinase 2-alfa) merupakan molekul penting dalam mengatur kaskade sinyal hematopoiesis yang terkait dalam mendorong pertumbuhan beberapa tumor darah. Senyawa ligan alami (CX-4945) dari reseptor CK2-α yang merupakan senyawa turunan alkaloid naftiridin berdasarkan beberapa penelitian yang telah dilakukan baik secara in vitro maupun secara in vivo terbukti memiliki aktivitas dalam menghambat sel-sel penyebab kanker, khususnya protein CK2-α pada kanker leukemia. Tujuan: Mengkaji interaksi dan afinitas senyawa turunan naftiridin terhadap reseptor CK2-α serta prediksi toksisitasnya sehingga menjadi alternatif pengobatan leukemia dengan resiko efek samping yang minimum. Metodologi: Tahapan studi yang dilakukan antara lain pengkajian parameter fisikokimia, meliputi penetapan koefisien partisi (CLogP), bobot molekul (BM), jumlah donor dan akseptor ikatan hidrogen, jumlah rotasi ikatan, energi HOMO-LUMO, lalu dilakukan analisis interaksi ligan uji terhadap reseptor CK2-α melalui simulasi molecular docking dan molecular dynamic serta prediksi toksisitasnya. Validasi docking dilakukan dengan me-redocking ligan alami CX-4945 dari reseptor CK2-α (kode PDB: 3PE1), diperoleh nilai RMSD sebesar 0,358 Å. Hasil: Pada simulasi molecular docking senyawa turunan naftiridin terhadap reseptor CK2-α dengan Autodock didapatkan 10 ligan uji terbaik dengan nilai energi bebas ikatan (∆G) dan nilai konstanta inhibisi (Ki) yang rendah. Sebelum dilakukan simulasi molecular dynamic, 10 ligan uji dan reseptor target dipreparasi dengan pembuatan topologi. Hasil simulasi molecular dynamic 10 ligan uji terbaik terhadap reseptor CK2-α dengan Gromacs selama 10 nanodetik menunjukkan nilai RMSD dan RMSF yang rendah ditandai dengan kecenderungan grafik yang cukup konstan, dimana nilai RMSD untuk ligan uji 4-Metilaaptamin sebesar 1,4 Å dan nilai RMSF untuk ligan uji Lopokladin A sebesar 1,5 Å menunjukkan kestabilan yang cukup baik diantara ligan uji lainnya. Sedangkan prediksi toksisitas dengan ADMET Predictor menunjukkan bahwa ligan uji Kloronaftiridin diprediksi memiliki resiko toksisitas paling rendah dibandingkan ligan uji lainnya. Berdasarkan hasil penelitian tersebut, diketahui bahwa 4-Metilaaptamin merupakan kandidat senyawa inhibitor CK2-α yang paling berpotensi dengan afinitas tertinggi dan resiko toksisitas yang rendah.
<p class="western" style="margin-bottom: 0in; line-height: 100%;" align="justify"><span style="font-family: Times New Roman, serif;"><span style="font-size: small;"><span lang="id-ID">Reseptor SIRT3 </span></span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;">(sirtuin-3) </span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;"><span lang="id-ID">diketahui mampu menjaga level Spesies Oksigen Reaktif / </span></span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;"><em>Reactive Oxygen Species (ROS)</em></span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;"><span lang="id-ID"> pada jumlah yang sesuai </span></span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;">dalam</span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;"><span lang="id-ID"> menjaga proliferasi sel dan sejumlah agresifitas fenotip yang mampu mencegah apoptosis dan </span></span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;">menyebabkan </span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;"><span lang="id-ID">karsinogenesis. Pengujian </span></span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;"><span lang="id-ID"><em>in vitro </em></span></span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;">menunjukkan </span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;"><span lang="id-ID">bahwa senyawa stilben </span></span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;"><span lang="id-ID">4</span></span></span><span><span lang="ar-SA"><span style="font-family: Times New Roman;"><span style="font-size: small;"><span lang="he-IL"><em>׳</em></span></span></span></span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;"><span lang="id-ID">-bromo-resveratrol memiliki potensi kuat dalam menghambat aktivitas SIRT3 pada sel melanoma manusia dengan mencegah proliferasi sel dan menginduksi apoptosis. </span></span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;">Penelitian ini bertujuan untuk mengkaji interaksi dan afinitas senyawa derivat stilben terhadap reseptor hSIRT3 melalui simulasi </span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;"><em>docking</em></span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;">. Interaksi yang terjadi dipelajari melalui simulasi dinamika molekul yang menggambarkan kestabilan interaksi antara protein ‒ ligan. Prediksi toksisitas dilakukan guna mengkaji keamanan dan toksisitasnya terhadap tubuh manusia. Validasi </span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;"><em>docking</em></span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;"> dilakukan dengan me-</span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;"><em>redocking</em></span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;"> ligan alami (</span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;"><span lang="id-ID">4</span></span></span><span><span lang="ar-SA"><span style="font-family: Times New Roman;"><span style="font-size: small;"><span lang="he-IL"><em>׳</em></span></span></span></span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;"><span lang="id-ID">-bromo-resveratrol</span></span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;">) dari reseptor target hSIRT3 (kode PDB 4C7B) dengan hasil nilai RMSD 1,88 Å. Simulasi </span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;"><em>docking </em></span></span><span style="font-family: Times New Roman, serif;"><span style="font-size: small;">terhadap 20 senyawa uji diperoleh 10 senyawa uji dengan afinitas terbaik yang akan dilanjutkan ke tahapan simulasi dinamika molekul. Persiapan file topologi kesepuluh senyawa uji dan protein target dilakukan sebelum simulasi dinamika molekul. Hasil simulasi dinamika molekul selama 10 ns menunjukkan bahwa senyawa Tetrahidroksistilben-2, Arahipin-10 dan Gnetin-L memiliki kestabilan interaksi yang baik terhadap hSIRT3 yang ditunjukkan oleh kecenderungan grafik RMSD yang konstan selama simulasi. Hasil prediksi toksisitas 20 senyawa uji diperoleh bahwa sebesar 83% senyawa uji tidak menimbulkan toksisitas.Berdasarkan penelitian tersebut, diketahui bahwa senyawa Tetrahidroksistilben-2 paling berpotensi menjadi kandidat senyawa inhibitor hSIRT3 dengan afinitas tertinggi dan resiko toksisitas yang minimal.</span></span></p>
Objective: Prostate cancer is the second most common cancer in men. One of the efforts in the treatment of prostate cancer is by inhibiting histone lysine demethylase. Derivative compounds of coumarine, N-oxalylglycine, organoselenium, organosulfur, and pyridine have been reported to be active against two types of histone lysine demethylase (KDM) enzymes, KDM4E and KDM5B. This study aims to study the interactions of these derivatives with KDM. Methods:In this study, we performed computational studies, including molecular docking and molecular dynamics (MDs) simulations, and toxicity prediction, to assess the compounds' activities toward three other KDM enzymes, KDM1A, KDM4A, and KDM4C.Results: Molecular docking simulations showed that a derivative compound of N-oxalylglycine, (R)-3-(4-[benzyloxy]phenyl)-2-(carboxyformamido) propanoic acid, and a derivative compound of pyridine, 3-(4-methoxybenzylamino)pyridine-2,4-dicarboxylic acid, has the highest affinity toward KDM. These results were confirmed in MDs studies which showed strong interactions at the active site of the five receptors. Toxicity prediction results show that the derivative compounds of coumarine, N-oxalylglycine, organoselenium, organosulfur, and pyridine are classified in category (high class), which suggests that the safety is not guaranteed, but is likely, not carcinogenic and nongenotoxic. Conclusion:Several coumarin, N-oxalylglycine, organoselenium, organosulfur, and pyridine derivative compounds are predicted to be able to interact strongly with KDM. The results in this study are useful for further studies in the development of novel anticancer drugs that target KDM.
PARTNER VILLAGE IN FAMILY MEDICINE PLANT CULTIVATION TOWARDS CIBIRU WETAN VILLAGE AS A HERBAL CENTER. The area of Cibiru Wetan Village is a farming area because besides the limited water supply, the land is hilly. With the initiative and participation of women farmer groups which had so many achievements and skills, it was necessary to explore the potential that could provide a new icon for Cibiru Wetan Village. The purpose of the activity was to socialize and practice the cultivating of the medicinal plants carried out by a group of women farmers with simple and effective technology and finally able to become a center of dried herbs production. The method used in the cultivation program for medicinal plants was divided into three stages. The first stage was to provide material counseling on family medicinal plants including the understanding of the benefits of the plant, the second stage was to provide an explanation or training in planting family medicinal plants and the last stage or third stage was to practice directly in planting these medicinal plants. The results showed a positive understanding of both groups for both the socialization and counseling stages as well as for the practice of medicinal plants cultivation. It could be concluded, the partner village activities in medicinal plants cultivation could improve the understanding of the target group.
Cancer is a disease involving genetic factors in its pathogenesis. The increase of cell survival as a result of genetic changes, which prevent apoptosis such as Bcl2 (B-cell lymphoma-2) activation, will cause the tumor to grow. The overexpression of Bcl2 in small cell lung cancer should be inhibited. This study aims to screen natural products that can inhibit Bcl2 overexpression in lung cancer using pharmacophore- and molecular docking-based virtual screening to ZINC Natural Product database. The validation of pharmacophore-based virtual screening to the three features of the pharmacophore model (2 hydrophobic interactions and 1 hydrogen bond donor) showed that the AUC, EF, Se, Sp, ACC, and GH values were 0.57, 3.8, 0.101, 0.957, 0.936, and 0.149, respectively. On the other hand, the validation of molecular docking-based virtual screening showed that the RMSD values of Vina Wizard and AutoDock Wizard were 1.3Å and 1.9Å, respectively. The pharmacophore model virtual screening first obtained 6,615 compounds, and then the molecular docking-based virtual screening finally gained 255 compounds whose values of ΔG and Ki were lower than those of the native ligand. It was concluded that the virtual screening could yield as many as 255 potential anti-lung cancer drug candidates. Keywords: B-cell lymphoma 2 inhibitors, molecular docking, pharmacophore modeling, virtual screening
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