DESAIN TURUNAN FENOKSIPIRIDIN SEBAGAI INHIBITOR PROTOPORFIRINOGEN OKSIDASE DENGAN QSAR DAN MOLECULAR DOCKING - Chandra Pratama Putra, - (2022)
ABSTRAK Herbisida sangat penting digunakan dalam produksi tanaman untuk melindungi mereka dari persaingan dengan gulma untuk meningkatkan hasil panen dan kualitas tanaman. Herbisida inhibitor protoporfirinogen oksidase (PPO, EC 1.3.3.4) bekerja pada enzim protoporfirinogen oksidase, yang mengkatalisis oksidasi protoporfirinogen IX menjadi protoporfirin IX. Penelitian ini mengkaji serangkaian turunan fenoksipiridin baru yang didesain sebagai inhibitor protoporfirinogen oksidase. Quantitative Structure-Activity Relationship (QSAR) digunakan untuk menentukan mode pengikatan dan stabilitas strukturalnya sebagai struktur inhibitor protoporfirinogen oksidase untuk membuat inhibitor protoporfirinogen oksidase berdasarkan senyawa yang disintesis. Sebanyak 21 senyawa turunan fenoksipiridin yang mengandung kumarin dan aktivitas (IC50) yang diperoleh dari penelitian sebelumnya digunakan dalam penelitian ini. Struktur dioptimasi menggunakan metode semiempirik Austin Model 1 (AM1) dan pemodelan QSAR menggunakan metode Multiple Linear Regression (MLR). Diperoleh dua model persamaan QSAR dengan akurasi pemodelan yang baik (R_tr^2 elektronik = 0,8208; R_tr^2 3D = 0,8892) dan memiliki kemampuan untuk memprediksi aktivitas biologis berupa log IC50 prediksi (R_val^2 elektronik = 0,9575; R_val^2 3D = 0,9795). Senyawa turunan fenoksipiridin baru yang paling berpotensi sebagai inhibitor protoporfirinogen oksidase berdasarkan interaksi hasil docking yaitu senyawa A7 dengan docking score -6,83 kkal/mol, senyawa A8 sebesar -6,88 kkal/mol, dan B7 sebesar -6,71 kkal/mol. ABSTRACT Herbicides are very important used in crop production to protect them from competition with weeds to increase crop yields and quality of crop. The herbicide protoporphyrinogen oxidase (PPO, EC 1.3.3.4) acts on the enzyme protoporphyrinogen oxidase, which catalyzes the oxidation of protoporphyrinogen IX to protoporphyrin IX. In this study, a series of new phenoxypyridine derivatives were developed as protoporphyrinogen oxidase inhibitors. In this case, Quantitative Structure-Activity Relationship (QSAR) was used to determine the binding mode and its structural stability as a structure of a protoporphyrinogen oxidase inhibitor, to make protoporphyrinogen oxidase inhibitors based on the synthesized compounds. A total of 21 phenoxypyridine derivatives compounds containing coumarin and activity (IC50) obtained from previous studies were used in this study. The structure was optimized using the Austin Model 1 (AM1) semi-empirical method and QSAR modeling using the Multiple Linear Regression (MLR) method. Two models of QSAR equations were obtained with good accuracy (R_tr^2 electronic = 0.8208, R_tr^2 3D = 0.8892) and have the ability to predict biological activity in the form of predictive log IC50 (R_val^2 electronic = 0.9575, R_val^2 3D = 0.9795). The new phenoxypyridine derivatives that have the most potential as protoporphyrinogen oxidase inhibitors based on the interaction of the docking results are compound A7 with a docking score of -6.83 kcal/mole, compound A8 of -6.88 kcal/mole, and B7 of -6.71 kcal/mole.