eprintid: 137370 rev_number: 64 eprint_status: archive userid: 217549 dir: disk0/00/13/73/70 datestamp: 2025-09-15 03:50:29 lastmod: 2025-09-15 03:50:29 status_changed: 2025-09-15 03:50:29 type: thesis metadata_visibility: show creators_name: Lydzikri Astuti, - creators_name: Iqbal Musthapa, - creators_name: Ade Danova, - creators_nim: NIM2316585 creators_nim: NIDN0023127503 creators_nim: - creators_id: lydzikri@upi.edu creators_id: iqbalm@upi.edu creators_id: adedanova@itb.ac.id contributors_type: http://www.loc.gov/loc.terms/relators/THS contributors_type: http://www.loc.gov/loc.terms/relators/THS contributors_name: Iqbal Musthapa, - contributors_name: Ade Danova, - contributors_nidn: NIDN0023127503 contributors_nidn: - contributors_id: iqbalm@upi.edu contributors_id: adedanova@itb.ac.id title: SINTESIS DAN EVALUASI TURUNAN GENISTEIN SEBAGAI INHIBITOR α-GLUKOSIDASE UNTUK TERAPI DIABETES TIPE 2 ispublished: pub subjects: QD subjects: RC subjects: RM subjects: RS divisions: Kim_S2 full_text_status: restricted keywords: antidiabetes, dinamika molekul, genistein, inhibitor α-glukosidase, penambatan molekul. antidiabetic, genistein, molecular docking, molecular dynamics, genistein, α-glucosidase inhibitor. note: https://scholar.google.com/citations?user=_MJFAv0AAAAJ&hl=en&oi=ao ID SINTA Dosen Pembimbing: Iqbal Musthapa: 5979687 Ade Danova: 6837986 abstract: Diabetes melitus tipe 2 adalah penyakit degeneratif dengan prevalensi global yang terus meningkat, dimana Indonesia menempati peringkat kelima dunia dengan kasus diabetes tertinggi berdasarkan laporan International Diabetes Federation pada tahun 2024. Salah satu pendekatan terapi diabetes tipe 2 adalah penghambatan aktivitas α-glukosidase, namun inhibitor yang tersedia saat ini memiliki efek samping ketergantungan terhadap dosis dan ketidaknyamanan pada saluran pencernaan. Genistein (1), isoflavon alami dari kedelai dilaporkan memiliki berbagai aktivitas biologis, salah satunya sebagai antidiabetes. Tetapi, genistein memiliki bioavailabilitas yang rendah. Berdasarkan hal tersebut, penelitian yang dilakukan bertujuan untuk mensintesis dan mengevaluasi turunan genistein sebagai kandidat inhibitor α-glukosidase. Modifikasi struktur dilakukan melalui reaksi benzilasi, eterifikasi, nitrasi, dan halogenasi. Karakterisasi produk sintesis dilakukan dengan NMR (Nuclear Magnetic Resonance) dan MS (Mass Spectrometry), sedangkan evaluasi bioaktivitas dilakukan melalui pendekatan in vitro serta in silico (penambatan molekul dan dinamika molekular). Berdasarkan hasil sintesis yang telah dilakukan, berhasil didapatkan lima senyawa turunan genistein, yaitu 7-O-benzilgenistein (3), 7-O- (metil-2-asetoksi)genistein (4), 3'-nitrogenistein (5), 6,8-dibromogenistein (6) dan 6,8-diklorogenistein (7). Rendemen masing-masing senyawa secara berutan sebesar 8,6% (3), 15,7% (4), dan 0,7% (5). Senyawa 6 dan 7 memiliki rendemen sebesar 32,7% dan 5,5% untuk sintesis menggunakan Oxone®, sedangkan sintesis menggunakan H2O2 masing-masing rendemen sebesar 84,3% dan 43,3%. Hasil uji in vitro menunjukkan bahwa 7-O-benzilgenistein (3) memiliki nilai IC50 sebesar 6,4 µM, mendekati nilai penghambatan oleh genistein (1). Selain itu, hasil uji in silico juga menunjukkan bahwa 7-O-benzilgenistein (3) memiliki afinitas ikatan terbaik, yaitu sebesar -7,8 kkal/mol terhadap akarbosa (2). Simulasi dinamika molekuler menunjukkan seluruh senyawa hasil sintesis memiliki kestabilan yang lebih baik dari akarbosa (2). Hasil ini menunjukkan bahwa modifikasi struktur genistein (1) dapat meningkatkan potensi bioaktivitasnya sebagai kandidat inhibitor α-glukosidase. Type 2 diabetes mellitus is a degenerative disease with an increasing global prevalence. According to the International Diabetes Federation’s 2024 report, Indonesia ranks fifth worldwide in terms of diabetes cases. One therapeutic approach for type 2 diabetes involves inhibiting α-glucosidase activity; however, current inhibitors often cause dose-dependent side effects and gastrointestinal discomfort. Genistein (1), a natural isoflavone derived from soybeans, has been reported to exhibit various biological activities, including antidiabetic properties. Nevertheless, its bioavailability remains low. Based on this, the present study aims to synthesize and evaluate genistein derivatives as potential α-glucosidase inhibitors. Structural modifications were carried out via benzylation, etherification, nitration, and halogenation reactions. The synthesized products were characterized using Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS), while bioactivity was assessed through both in vitro and in silico approaches, including molecular docking and molecular dynamics simulations. Five genistein derivatives were successfully synthesized: 7-O-benzylgenistein (3), 7-O-(2- acetoxymethyl)genistein (4), 3′-nitrogenistein (5), 6,8-dibromogenistein (6), and 6,8-dichlorogenistein (7). The yields of compounds 3, 4, and 5 were 8.6%, 15.7%, and 0.7%, respectively. Compound 6 and 7 were synthesized using two oxidation methods, Oxone® and H2O2, yielding 32,7% and 5,5% for Oxone® and 84,3% and 43,4% for H2O2. In vitro assays revealed that 7-O-benzylgenistein (3) exhibited an IC₅₀ value of 6.4 µM, comparable to that of genistein (1). Furthermore, in silico studies showed that 7-O-benzylgenistein (3) had the strongest binding affinity (-7.8 kcal/mol) to acarbose (2). Molecular dynamics simulations indicated that all synthesized compounds demonstrated better stability than acarbose (2). These findings suggest that structural modification of genistein (1) can enhance its bioactive potential as a candidate α-glucosidase inhibitor. date: 2025-08-25 date_type: published institution: Universitas Pendidikan Indonesia department: KODEPRODI47102#Kimia_S2 thesis_type: masters thesis_name: mphil official_url: https://repository.upi.edu/ related_url_url: https://perpustakaan.upi.edu/ related_url_type: org citation: Lydzikri Astuti, - and Iqbal Musthapa, - and Ade Danova, - (2025) SINTESIS DAN EVALUASI TURUNAN GENISTEIN SEBAGAI INHIBITOR α-GLUKOSIDASE UNTUK TERAPI DIABETES TIPE 2. S2 thesis, Universitas Pendidikan Indonesia. document_url: http://repository.upi.edu/137370/1/T_KIM_2316585_Title.pdf document_url: http://repository.upi.edu/137370/2/T_KIM_2316585_Chapter1.pdf document_url: http://repository.upi.edu/137370/3/T_KIM_2316585_Chapter2.pdf document_url: http://repository.upi.edu/137370/4/T_KIM_2316585_Chapter3.pdf document_url: http://repository.upi.edu/137370/5/T_KIM_2316585_Chapter4.pdf document_url: http://repository.upi.edu/137370/6/T_KIM_2316585_Chapter5.pdf document_url: http://repository.upi.edu/137370/7/T_KIM_2316585_Chapter6.pdf document_url: http://repository.upi.edu/137370/8/T_KIM_2316585_Appendix.pdf