Penelusuran Senyawa Inhibitor Dipeptidyl Peptidase-4 (DPP-4 Inhibitors atau Gliptin) Potensial untuk Diabetes Melitus Tipe 2 melalui Pendekatan In Silico dengan Evaluasi Profil ADME via SwissADME

Authors

Apriyani Pramudiyawati Yunar Akademi Farmasi Persada

DOI:

Abstract

This study aims to identify the potential of in silico methods as a rapid and cost-effective approach for the initial screening of DPP-4 inhibitor candidates, as well as to identify compounds that meet drug-likeness criteria and exhibit good ADME profiles. The methods used include compound discovery, physicochemical property analysis, drug-likeness prediction based on Lipinski's Rule of Five, and ADME profile evaluation using the SwissADME platform. The results indicate that Sitagliptin and Linagliptin have good drug-likeness profiles, comply with Lipinski's Rule of Five, and exhibit ADME characteristics that support drug development. The conclusions of this study confirm that the in-silico approach is effective for the initial screening of drug candidates, but further experimental validation is required to ensure their activity and safety.

Keywords: ADME, In Silico, DPP-4 Inhibitor, Drug-Likeness, SwissADME, Type 2 Diabetes Mellitus.

References

Arief, I., Hairunnisa, H. (2022). Profil ADME dari Entitas Molekul Baru yang Disetujui oleh FDA Tahun 2021: Suatu Kajian In Silico. JAMBURA: Journal of Chemistry. 4(2). 1–11. https://doi.org/10.37905/jambchem.v4i2.15257

Asnawi, A., Mieldianisa, S., Aligita, W., Yuliantini, A., Febrina, E. (2024). Integrative computational approaches for designing novel alpha-glucosidase inhibitors based on curculigoside A derivatives: Virtual screening , molecular docking, and molecular dynamics. JHP: Journal of Herbmed Pharmacology. 13(2). 308–323. https://doi.org/10.34172/jhp.2024.49407

Balogun, F. O., et al. (2022). Cheminformatics identification and validation of dipeptidyl peptidase-IV modulators from shikimate pathway-derived phenolic acids. Journal of Biomolecular Structure and Dynamics. https://doi.org/10.1080/07391102.2022.2123457

Baziar, L., Emami, L., Rezaei, Z., Solhjoo, A., Sakhteman, A., & Khabnadideh, S. (2024). Design, synthesis, biological evaluation and computational studies of 4-aminopiperidine-3,4-dihydroquinazoline-2-uracil derivatives as promising antidiabetic agents. Scientific Reports, 14. 26538. https://doi.org/10.1038/s41598-024-77481-9

Epelde F. (2024). Transforming Diabetes Care: The Expanding Role of DPP-4 Inhibitors in Cardiovascular and Renal Protection. Medicina (Kaunas, Lithuania), 60(11). 1793. https://doi.org/10.3390/medicina60111793

Hakiki, A., Andika, A., Rahmawati, R. (2024). Studi Molecular Docking dan Prediksi ADMET Senyawa Turunan Kurkumin Sebagai Inhibitor Kasein Kinase 2-α. Lumbung Farmasi: Jurnal Ilmiah Kefarmasian. 5(2). https://doi.org/10.31764/lf.v5i2.22563

Istrate, D., et al. (2022). Natural compounds as DPP-4 inhibitors: 3D similarity search, ADMETox and molecular docking approaches. Symmetry, 14(1842). 1–30. https://doi.org/10.3390/sym14091842

Khan, H., Jan, F., Shakoor, A., Khan, A., Alasmari, A. F., Alasmari, F., Ullah, S., Harrasi, A. Al, Khan, M., & Ali, S. (2024). Design , synthesis , molecular docking study , and α ‑ glucosidase inhibitory evaluation of novel hydrazide–hydrazone derivatives of 3, 4‑dihydroxyphenylacetic acid. Scientific Reports. 4. 11410. https://doi.org/10.1038/s41598-024-62034-x

Khedraoui, M., Abchir, O., Nour, H., Yamari, I., Errougui, A., Samadi, A., & Chtita, S. (2024). An In Silico Study Based on QSAR and Molecular Docking and Molecular Dynamics Simulation for the Discovery of Novel Potent Inhibitor against AChE. Pharmaceuticals. 17(7). 830. https://doi.org/10.3390/ph17070830

Łupina, M., Wąsik, A., Baranowska-Bosiacka, I., Tarnowski, M., Słowik, T., Listos, P., Kotlińska, J., Kosik-Bogacka, D., Gutowska, I., & Listos, J. (2024). Acute and Chronic Exposure to Linagliptin, a Selective Inhibitor of Dipeptidyl Peptidase-4 (DPP-4), Has an Effect on Dopamine, Serotonin and Noradrenaline Level in the Striatum and Hippocampus of Rats. International Journal of Molecular Sciences. 25(5). 3008. https://doi.org/10.3390/ijms25053008

Nakamura, R., Yoshikado, T., Aoki, Y., Sigiyama, Y., Chiba, K. (2024). Elucidation of DPP- 4 involvement in systemic distribution and renal reabsorption of linagliptin by PBPK modeling with a cluster Gauss – Newton method. Juni. CTS: Clinical and Translational Science. 17(10). 1–14. https://doi.org/10.1111/cts.70047

Olivares, M., Hernández-Calderón, P., Cárdenas-Brito, S., Liébana-García, R., Sanz, Y., & Benítez-Páez, A. (2024). Gut microbiota DPP4-like enzymes are increased in type-2 diabetes and contribute to incretin inactivation. Genome biology, 25(1), 174. https://doi.org/10.1186/s13059-024-03325-4

Pramudiyawati, A., Putri, D. E., & Wilapangga, A. (2024). Skrining Studi in Silico Potensi Farmakokinetika dan Toksisitas Ekaliptus. 4(1), 39–46. https://doi.org/10.37311/ijpe.v4i1.24493

Sari, S. W., Wilapangga, A., Sari, A. N., & Astriani, S. (2023). Studi In Silico Potensi Farmakokinetik Dua Senyawa Dari Tanaman Kenaf (Hibiscus cannabinus L) Untuk Prediksi Toksisitas. Jurnal Bina Cipta Husada: Jurnal Kesehatan Dan Science 19 (2), 70-79.

Shah, B. R., Bajaj, H. S., Butalia, S., Dasgupta, K., Bsp, D. T. E., Jain, R., Leung, K., Coe, C., Bsp, K. M., & Bsp, S. S. (2024). Pharmacologic Glycemic Management of Type 2 Diabetes in Adults-2024 Update Diabetes Canada Clinical Practice Guidelines Expert Working Group: Canadian Journal of Diabetes. 48(7). 415–424. https://doi.org/10.1016/j.jcjd.2024.08.002

Sulastri, T., & Suwitono, M. R. (2024). In-Silico ADMETox Profiling of Quercetin Derivatives. 11th International Scholars Conference. 11(6). 1597-1609. https://doi.org/10.35974/isc.v11i6.3709

Wilapangga, A., Noordam, E. R., & Yudianto, D., Nurfaidlillah, N., Amelia, E. A., Yunar, A. P., Putri, D. E. (2025). Analisis in Silico Pengaruh Kurkumin Terhadap Stabilitas Protein Frataxin. JSSCR: Journal Syifa Science Clinical Research. 7(1). https://doi.org/10.37311/jsscr.v7i1.29588