Electronic Theses and Dissertation

Resistensi kemoterapi dan radioterapi seringkali muncul pada stadium akhir dari karsinoma nasofaring (knf). penurunan respon knf terhadap kemoterapi dan radioterapi terjadi karena penghambatan apoptosis sel kanker oleh protein b-cell lymphoma-2 (bcl-2). oleh karena itu, penghambatan terhadap protein bcl-2 dapat menjadi pendekatan yang ampuh untuk pengobatan knf melalui regulasi apoptosis. di sisi lain, pogostemon cablin benth. dilaporkan memiliki sifat anti-kanker, namun belum banyak penelitian yang berkaitan dengan knf. penelitian ini bertujuan untuk mengeksplorasi potensi senyawa bioaktif dari p. cablin sebagai inhibitor protein anti-apoptosis bcl-2 menggunakan pendekatan in silico. senyawa bioaktif dari p. cablin diperoleh dari database knapsack dan dilakukan screening untuk melihat efek penghambatan pada protein bcl-2 melalui molecular docking dengan parameter yang diuji berupa binding energy, hidrofobisitas, dan interaksi kimia menggunakan perangkat lunak pyrx 0.9.5 yang digabungkan dengan molecular dynamics simulation menggunakan perangkat lunak yasara versi 21 dengan parameter yang diuji yaitu root mean square deviation (rmsd) ligan, rmsd ligan movement, rmsd backbone, binding energy, jumlah ikatan hidrogen dan root mean square fluctuation (rmsf). berdasarkan hasil molecular docking diperoleh bahwa apigenin 7-(6"-p-coumarylglucoside) memiliki sifat penghambatan yang sangat baik terhadap protein bcl-2 dengan nilai afinitas energi -9.9 kkal/mol dan jumlah interaksi yang terbentuk sebanyak 21 ikatan. tiga senyawa yang memiliki hasil docking paling baik yaitu apigenin 7-(6"-p-coumarylglucoside), rhamnetin, dan apigenin kemudian dilanjutkan untuk molecular dynamic simulation (mds). berdasarkan hasil mds diperoleh bahwa senyawa apigenin 7-(6"-p-coumarylglucoside) memiliki kestabilan paling baik ketika disimulasikan selama 50 ns pada kondisi tubuh manusia. secara umum, penelitian ini menunjukkan bahwa senyawa apigenin 7-(6"-p-coumarylglucoside) dari nilam memiliki potensi yang sangat baik sebagai inhibitor protein bcl-2 dan menjadi alternatif pengobatan terapi antikanker.

Chemotherapy and radiotherapy resistance often appears in the late stages of Nasopharyngeal Carcinoma (KNF). The decreased response of KNF to chemotherapy and radiotherapy occurs due to the inhibition of cancer cell apoptosis by B-Cell Lymphoma-2 (BCL-2) protein. Therefore, inhibition of BCL-2 protein could be a powerful approach for the treatment of KNF through apoptosis regulation. On the other hand, Pogostemon cablin Benth. is reported to have anti-cancer properties, but there have not been many studies related to KNF. This study aims to explore the potential of bioactive compounds from P. cablin as inhibitors of the anti-apoptotic protein BCL-2 using an in silico approach. Bioactive compounds from P. cablin were obtained from the KNApSAcK database and screened to see the inhibitory effect on BCL-2 protein through molecular docking with parameters tested in the form of binding energy, hydrophobicity, and chemical interactions using PyRx 0.9.5 software which was combined with molecular dynamics simulation using YASARA software version 21 with the tested parameters of ligand root mean square deviation (RMSD), ligand movement RMSD, backbone RMSD, binding energy, number of hydrogen bonds and Root Mean Square Fluctuation (RMSF). Based on the molecular docking results, apigenin 7-(6"-p-coumarylglucoside) has excellent inhibitory properties against BCL-2 protein with an affinity energy value of -9.9 kcal/mol and the number of interactions formed as many as 21 bonds. Three compounds that have the best docking results are apigenin 7-(6"-p-coumarylglucoside), rhamnetin, and apigenin and then continued for molecular dynamic simulation (MDS). Based on the MDS results, it was found that apigenin 7-(6"-p-coumarylglucoside) compound had the best stability when simulated for 50 ns in human body conditions. In general, this study shows that Apigenin 7-(6"-p-coumarylglucoside) compound from patchouli has excellent potential as a BCL-2 protein inhibitor and an alternative anticancer therapy treatment.