KAJIAN IN SILICO DAN IN VITRO SENYAWA TURUNAN ASAM SINAMAT SEBAGAI PENGHAMBAT ENZIM TIROSINASE

ABSTRAK Reski Ekawaty. Kajian In Silico dan In Vitro Senyawa Turunan Asam Sinamat sebagai Penghambat Enzim Tirosinase (dibimbing oleh Muhammad Aswad and Yusnita Rifai) Latar Belakang. Turunan asam sinamat menarik perhatian sebagai kandidat inhibitor tirosinase karena kemiripan strukturnya dengan substrat fenolik dalam sintesis melanin. Tirosinase merupakan target terapi yang penting pada gangguan hiperpigmentasi. Tujuan. Penelitian ini bertujuan untuk mengidentifikasi dan mengkarakterisasi turunan asam sinamat yang berpotensi sebagai inhibitor tirosinase melalui pendekatan komputasi dan eksperimental. Metode. Sepuluh turunan asam sinamat disaring menggunakan pendekatan komputasional melalui molecular docking dan simulasi dinamika molekuler untuk memprediksi afinitas ikatan, interaksi utama, dan stabilitas kompleks. Profil ADMET dianalisis untuk menilai kelayakan pengembangan obat dan parameter keamanan. Berdasarkan hasil tersebut, enam senyawa dipilih untuk uji in vitro penghambatan tirosinase menggunakan substrat L-DOPA. Hasil. 4-Metil sinamat menunjukkan afinitas pengikatan tertinggi (ΔG = –6,2 kkal/mol) dan membentuk ikatan hidrogen stabil dengan residu His243, Met257, dan Asn240. Simulasi dinamika molekuler mengonfirmasi stabilitas kompleks dengan nilai RMSD di bawah 3 Å selama 100 ns. Prediksi ADMET menunjukkan penyerapan yang baik dan toksisitas rendah untuk sebagian besar senyawa. Dari enam senyawa yang diuji, 3,4-Dimethoxy Cinnamic Acid menunjukkan aktivitas penghambatan terbaik dengan nilai IC₅₀ sebesar 36,29 µg/mL. Senyawa lain seperti 4-Methyl Cinnamic Acid, dan Cinnamic Acid, menunjukkan aktivitas sedang. Kesimpulan. Korelasi antara prediksi komputasi dan data eksperimental menunjukkan bahwa skrining in silico dapat diandalkan untuk penemuan senyawa bioaktif. 3,4-Dimethoxy Cinnamic Acid memiliki potensi kuat sebagai senyawa utama dalam pengembangan inhibitor tirosinase untuk terapi hiperpigmentasi. ABSTRACT Reski Ekawaty. In Silico And In Vitro Investigation Of Cinnamic Acid Derivatives As Tyrosinase Enzyme Inhibitors (supervised by Muhammad Aswad and Yusnita Rifai). Background. Cinnamic acid derivatives have gained interest as potential tyrosinase inhibitors due to their structural similarity to phenolic substrates involved in melanin synthesis. Tyrosinase plays a crucial role in hyperpigmentation disorders, making it a promising therapeutic target. Objectives. This study aimed to identify and characterize cinnamic acid derivatives with tyrosinase inhibitory potential using a combination of computational and experimental approaches. Methods. Ten cinnamic acid derivatives were screened using a computational approachinvolving molecular docking and molecular dynamics simulations to predict binding affinity, key interactions, and complex stability. ADMET profiling was performed to assess drug-likeness and safety parameters. Based on these results, six compounds were selected for in vitro tyrosinase inhibition assays using L-DOPA as a substrate. Results. Methyl Cinnamic Acid exhibited the highest binding affinity (ΔG = –6.2 kcal/mol) and formed stable hydrogen bonds with His243, Met257, and Asn240 residues. Molecular dynamics simulations confirmed the stability of the complex, with RMSD values remaining below 3 Å over 100 ns. ADMET predictions indicated good absorption and low toxicity for most of the tested compounds. Among the six evaluated compounds, 3,4-Dimethoxy Cinnamic Acid demonstrated the strongest inhibitory activity, with an IC₅₀ value of 36.29 µg/mL. Other compounds, such as 4-Methyl Cinnamic Acid and Cinnamic Acid, exhibited moderate activity. Conclusion. The correlation between computational predictions and experimental data suggests that in silico screening is a reliable approach for the discovery of bioactive compounds. 3,4-Dimethoxy Cinnamic Acid shows strong potential as a lead compound for the development of tyrosinase inhibitors for hyperpigmentation therapy