PEMODELAN MOLEKUL SENYAWA TURUNAN KOJIC ACID SERTA INTERAKSINYA DENGAN ENZIM TIROSINASE
Abstract
Studi HKSA dilakukan pada turunan kojyl thioether sebagai inhibitor tirosinase. Perhitungan prediktotr dilakukan menggunakan aplikasi hyperchem 8.0 dengan metode optimasi geometri semi-empirik PM3. Analisis regresi multilinier menggunakan SPSS 25.0 untuk mencari hubungan antara prediktor dan aktivitas senyawa turunan kojyl thioether sebagai inhibitor tirosinase. Model persamaan HKSA terbaik adalah :
pIC50 = -922.517 + 15.872*ELUMO – 436.654*qC4 – 209.509*qC5 + 1.0008*Eint
n = 14; m = 4; r = 0.949; R2 = 0.901; PRESS = 3.0469; q2 = 0.8246
Berdasarkan persamaan HKSA diatas didapatkan 4 senyawa baru turunun kojyl thioether yang bisa dijadikan sebagai analog inhibitor tirosinase yang baru. Parameter pemilihan senyawa tersebut karena memiliki aktivitas yang lebih baik sebagai inhibitor tirosinase dibandingkan senyawa penuntun, tidak hepatotoksik, tidak menimbulkan AMES Toxicity, tidak menimbulkan skin sensititasion dan LD50 pada tikus masuk kategori relative tidak membahayakan. Untuk melihat interaksi antara senyawa turunun kojyl thioether dengan enzim tirosinase dilakukan docking menggunakan Autodock vina yang visualisasinya menggunakan discovery studio 2020 client. Hasil docking menunjukkan bahwa semua senyawa setidaknya memiliki satu interaksi pada residu asam amino yang sama dengan native ligan. yaitu Val283.
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