Tinjauan Literatur: Pendekatan Komputasi Dan Sintesis Turunan Flavonoid Sebagai Kandidat Obat Antidiabetes Tipe 2
Literature Review: Computational Approaches And Synthesis Of Flavonoid Derivatives As Candidates For Type 2 Antidiabetic Drugs
Abstract
Diabetes melitus tipe 2 (DMT2) adalah gangguan metabolik kronis yang ditandai oleh resistensi insulin dan disfungsi sekresi insulin, mengakibatkan hiperglikemia. Terapi konvensional sering menimbulkan efek samping, sehingga diperlukan agen terapeutik yang lebih aman dan efektif. Flavonoid, senyawa polifenolik alami, telah menunjukkan potensi antidiabetik melalui penghambatan enzim penting dalam metabolisme glukosa, seperti ?-glukosidase, ?-amilase, DPP-4, dan SGLT-2. Tinjauan ini menganalisis perkembangan pendekatan komputasi—molecular docking, simulasi dinamika molekuler, dan prediksi ADMET—bersama dengan sintesis turunan flavonoid yang dimodifikasi secara struktural (misal triazole, isoxazole, trifluoromethyl) untuk meningkatkan afinitas dan aktivitas biologis. Hasil literatur menunjukkan bahwa flavonoid alami maupun sintetik mampu berinteraksi kuat dengan target enzim, dengan efektivitas yang mendekati obat kontrol seperti acarbose dan empagliflozin. Analisis struktur-aktivitas (SAR) menegaskan peran substituen tertentu dalam memperkuat interaksi H-bond dan hidrofobik di situs aktif enzim. Kombinasi strategi komputasi multitarget dan optimasi struktur flavonoid menawarkan pendekatan yang menjanjikan untuk pengembangan agen antidiabetik tipe 2 yang selektif, efektif, dan berisiko efek samping rendah. Validasi lebih lanjut melalui uji in vitro, in vivo, dan formulasi farmasetika sangat diperlukan untuk mendukung pengembangan kandidat flavonoid menuju tahap pra-klinis.
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