Araştırma Makalesi
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DOĞAL ALFA-GLUKOSİDAZ İNHİBİTÖRLERİNİ ANLAMAYA DOĞRU: HESAPLAMALI BİR ÇALIŞMA

Yıl 2024, Cilt: 48 Sayı: 1, 205 - 214, 20.01.2024
https://doi.org/10.33483/jfpau.1356028

Öz

Amaç: Şeker hastalığı dünya çapında yüz milyonlarca insanı etkileyen metabolik bir hastalıktır. Hastalık yetersiz insülin üretimi veya insülin direncinden kaynaklanan bozulmuş glukoz homeostazisinin neden olduğu hiperglisemi ile karakterizedir. Yemek sonrası kan şekeri seviyesini düşürmek amacıyla klinikte kullanılan α-glukosidaz inhibitörü ilaçlar bulunmaktadır. Ancak bu ilaçların yan etkileri olduğundan daha az yan etkili ve yüksek etkinliği olan yeni α-glukosidaz inhibitörlerinin keşfedilmesine ihtiyaç duyulmaktadır. Şeker hastalığıyla mücadelede doğal kaynaklı ürünlerin kullanımına olan ilgi giderek artmaktadır. Bu nedenle doğal kaynaklı α-glukosidaz inhibitörlerinin enzimi inhibe etme potansiyelleri hesaplamalı yöntemlerle araştırılmıştır.
Gereç ve Yöntem: Seçilmiş doğal kaynaklı α-glukosidaz inhibitörlerinin bağlanma potansiyeli, moleküler doking yoluyla araştırılmıştır. Daha sonra, en yüksek bağlanma potansiyeline sahip komplekslerin stabilitesi moleküler dinamik (MD) simülasyonu yoluyla değerlendirilmiştir.
Sonuç ve Tartışma: Moleküler doking çalışması bileşik 2'nin standart ilaç olan akarbozdan daha iyi bağlanma potansiyeline sahip olduğunu göstermiştir. Bileşik 7 ise standart ilaca benzer bağlanma potansiyeline sahipti. Ayrıca, test edilen bileşiklerin hepsi enzime karşı makul bağlanma potansiyeli sergilemelerine rağmen standart ilaçtan daha zayıf bağlandığı görülmüştür. MD simülasyonu da bileşik 2 ve 7'nin standart ilaca benzer stabiliteye sahip kompleksler verdiğini göstermiştir. Hesaplama yöntemlerin sonuçları araştırılan doğal kaynaklı inhibitörlerin enzime bağlanma yeteneğine sahip olduğunu ve stabil kompleksler oluşturduğunu ortaya çıkarmıştır. Bu nedenle bu bileşikler klinik kullanım için potansiyel α-glukosidaz inhibitörleri olabilir. Bu yüzden en yüksek bağlanma potansiyeline sahip bileşikler üzerinde daha fazla in vitro araştırma yapılması tavsiye edilir.

Kaynakça

  • 1. Alrefai, H., Allababidi, H., Levy, S., Levy, J. (2002). The endocrine system in diabetes mellitus. Endocrine, 18(2), 105-119. [CrossRef]
  • 2. Kashtoh, H., Baek, K.H. (2022). Recent updates on phytoconstituent alpha-glucosidase inhibitors: an approach towards the treatment of type two diabetes. Plants, 11(20), 20. [CrossRef] 3. Wilcox, G. (2005). Insulin and insulin resistance. Clinical Biochemist Reviews, 26(2), 19-39.
  • 4. Brajendra K.T., Arvind K.S. (2006). Diabetes mellitus: Complications and therapeutics. Medical Science Monitor, 12(7), RA130-147.
  • 5. Fan, W. (2017). Epidemiology in diabetes mellitus and cardiovascular disease. Cardiovascular Endocrinology, 6(1), 8-16.
  • 6. Watada, H., Tamura, Y. (2017). Impaired insulin clearance as a cause rather than a consequence of insulin resistance. Journal of Diabetes Investigation, 8(6), 723-725. [CrossRef]
  • 7. Singh, A., Singh, K., Sharma, A., Kaur, K., Kaur, K., Chadha, R., Bedi, P.M.S. (2023). Recent developments in synthetic α-glucosidase inhibitors: A comprehensive review with structural and molecular insight. Journal of Molecular Structure, 1281, 135115. [CrossRef]
  • 8. Ananya B., Sofia B. (2017). Therapeutic targets of type 2 diabetes: An overview. MOJ Drug Design Development and Therapy, 1(3), 60-64. [CrossRef]
  • 9. Dirir, A.M., Daou, M., Yousef, A.F., Yousef, L.F. (2022). A review of alpha-glucosidase inhibitors from plants as potential candidates for the treatment of type-2 diabetes. Phytochemistry Reviews, 21, 1049-1079. [CrossRef] 10. Mushtaq, A., Azam, U., Mehreen, S., Naseer, M.M. (2023). Synthetic α-glucosidase inhibitors as promising anti-diabetic agents: Recent developments and future challenges. European Journal of Medicinal Chemistry, 249, 115119. [CrossRef]
  • 11. Hedrington, M.S., Davis, S.N. (2019). Considerations when using alpha-glucosidase inhibitors in the treatment of type 2 diabetes. Expert Opinion on Pharmacotherapy, 20(18), 2229-2235. [CrossRef]
  • 12. Modak, M., Dixit, P., Londhe, J., Ghaskadbi, S., Paul A. Devasagayam, T. (2007). Indian herbs and herbal drugs used for the treatment of diabetes. Journal of Clinical Biochemistry and Nutrition, 40(3), 163-173. [CrossRef] 13. Muhammed, M.T., Aki-Yalcin, E. (2021). Pharmacophore modeling in drug discovery: Methodology and current status. Journal of the Turkish Chemical Society, Section A: Chemistry, 8(3), 759-772. [CrossRef]
  • 14. Fan, J., Fu, A., Zhang, L. (2019). Progress in molecular docking. Quantitative Biology, 7(2), 83-89. [CrossRef]
  • 15. Muhammed, M.T., Aki-Yalcin, E. (2024). Molecular docking: Principles, advances, and its applications in drug discovery. Letters in Drug Design and Discovery, 21(3), 480-495. [CrossRef]
  • 16. Auiewiriyanukul, W., Saburi, W., Kato, K., Yao, M., Mori, H. (2018). Function and structure of GH13_31 α-glucosidase with high α-(1→4)-glucosidic linkage specificity and transglucosylation activity. FEBS Letters, 592(13), 2268-2281. [CrossRef]
  • 17. Trott, O., Olson, A.J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. Journal of Computational Chemistry, 31(2), 455. [CrossRef]
  • 18. Arslan, G., Gökçe, B., Muhammed, M.T., Albayrak, Ö. (2023). Synthesis, DFT calculations, and molecular docking study of acetohydrazide-based sulfonamide derivatives as paraoxonase 1 inhibitors. ChemistrySelect, 8(10), e202204630. [CrossRef]
  • 19. Muhammed, M.T., Kökbudak Z., Akkoç S. (2023). Cytotoxic activities of the pyrimidine-based acetamide and isophthalimide derivatives: An in vitro and in silico studies. Molecular Simulation, 49(10), 982-992. [CrossRef]
  • 20. Gökçe, B., Muhammed, M.T. (2023). Evaluation of in vitro effect, molecular docking, and molecular dynamics simulations of some dihydropyridine-class calcium channel blockers on human serum paraoxonase 1 (hPON1) enzyme activity. Biotechnology and Applied Biochemistry, 70(5), 1707-1719. [CrossRef]
  • 21. Akman, S., Akkoc, S., Zeyrek, C.T., Muhammed, M.T., Ilhan, I.O. (2023). Density functional modeling, and molecular docking with SARS-CoV-2 spike protein (Wuhan) and omicron S protein (variant ) studies of new heterocyclic compounds including a pyrazoline nucleus. Journal of Biomolecular Structure and Dynamics, 41(22), 12951-12965. [CrossRef]
  • 22. Maity, D., Singh, D., Bandhu, A. (2023). Mce1R of Mycobacterium tuberculosis prefers long‑chain fatty acids as specific ligands: A computational study. Molecular Diversity, 27, 2523-2543. [CrossRef]

TOWARDS UNDERSTANDING NATURAL ALPHA-GLUCOSIDASE INHIBITORS: A COMPUTATIONAL STUDY

Yıl 2024, Cilt: 48 Sayı: 1, 205 - 214, 20.01.2024
https://doi.org/10.33483/jfpau.1356028

Öz

Objective: Diabetes mellitus is a metabolic disorder affecting hundreds of millions of people around the world. It is characterized by hyperglycemia caused by impaired glucose homeostasis that results from insufficient insulin production or insulin resistance. There are clinically available α-glucosidase inhibitor drugs that are used to decrease postprandial blood glucose level. However, these drugs have side effects that necessitated the discovery of new α-glucosidase inhibitors with less side effects and high potency. The interest in the use of natural products to deal with diabetes has been increasing. Therefore, the potential of natural α-glucosidase inhibitors to inhibit the enzyme was investigated through computational methods.
Material and Method: The binding potential of selected natural α-glucosidase inhibitors was investigated through molecular docking. Thereafter, the stability of the complexes with the highest binding potential were assessed through molecular dynamics (MD) simulation.
Result and Discussion: The molecular docking demonstrated that compound 2 had better binding potential than the standard drug, acarbose. Compound 7 had comparable binding potential to the standard drug. Furthermore, all the tested compounds exhibited a reasonable binding potential towards the enzyme but were weaker than the standard drug. The MD simulation demonstrated that compounds 2 and 7 gave complexes with similar stability to the standard drug. The overall computational results revealed that the natural inhibitors investigated had the ability to bind to the enzyme and formed stable complexes. Therefore, these compounds could be potential α-glucosidase inhibitors for clinical use. For this reason, further in vitro investigations on compounds with the highest binding potential is recommended.

Teşekkür

The numerical calculations reported in this paper were partially performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources).

Kaynakça

  • 1. Alrefai, H., Allababidi, H., Levy, S., Levy, J. (2002). The endocrine system in diabetes mellitus. Endocrine, 18(2), 105-119. [CrossRef]
  • 2. Kashtoh, H., Baek, K.H. (2022). Recent updates on phytoconstituent alpha-glucosidase inhibitors: an approach towards the treatment of type two diabetes. Plants, 11(20), 20. [CrossRef] 3. Wilcox, G. (2005). Insulin and insulin resistance. Clinical Biochemist Reviews, 26(2), 19-39.
  • 4. Brajendra K.T., Arvind K.S. (2006). Diabetes mellitus: Complications and therapeutics. Medical Science Monitor, 12(7), RA130-147.
  • 5. Fan, W. (2017). Epidemiology in diabetes mellitus and cardiovascular disease. Cardiovascular Endocrinology, 6(1), 8-16.
  • 6. Watada, H., Tamura, Y. (2017). Impaired insulin clearance as a cause rather than a consequence of insulin resistance. Journal of Diabetes Investigation, 8(6), 723-725. [CrossRef]
  • 7. Singh, A., Singh, K., Sharma, A., Kaur, K., Kaur, K., Chadha, R., Bedi, P.M.S. (2023). Recent developments in synthetic α-glucosidase inhibitors: A comprehensive review with structural and molecular insight. Journal of Molecular Structure, 1281, 135115. [CrossRef]
  • 8. Ananya B., Sofia B. (2017). Therapeutic targets of type 2 diabetes: An overview. MOJ Drug Design Development and Therapy, 1(3), 60-64. [CrossRef]
  • 9. Dirir, A.M., Daou, M., Yousef, A.F., Yousef, L.F. (2022). A review of alpha-glucosidase inhibitors from plants as potential candidates for the treatment of type-2 diabetes. Phytochemistry Reviews, 21, 1049-1079. [CrossRef] 10. Mushtaq, A., Azam, U., Mehreen, S., Naseer, M.M. (2023). Synthetic α-glucosidase inhibitors as promising anti-diabetic agents: Recent developments and future challenges. European Journal of Medicinal Chemistry, 249, 115119. [CrossRef]
  • 11. Hedrington, M.S., Davis, S.N. (2019). Considerations when using alpha-glucosidase inhibitors in the treatment of type 2 diabetes. Expert Opinion on Pharmacotherapy, 20(18), 2229-2235. [CrossRef]
  • 12. Modak, M., Dixit, P., Londhe, J., Ghaskadbi, S., Paul A. Devasagayam, T. (2007). Indian herbs and herbal drugs used for the treatment of diabetes. Journal of Clinical Biochemistry and Nutrition, 40(3), 163-173. [CrossRef] 13. Muhammed, M.T., Aki-Yalcin, E. (2021). Pharmacophore modeling in drug discovery: Methodology and current status. Journal of the Turkish Chemical Society, Section A: Chemistry, 8(3), 759-772. [CrossRef]
  • 14. Fan, J., Fu, A., Zhang, L. (2019). Progress in molecular docking. Quantitative Biology, 7(2), 83-89. [CrossRef]
  • 15. Muhammed, M.T., Aki-Yalcin, E. (2024). Molecular docking: Principles, advances, and its applications in drug discovery. Letters in Drug Design and Discovery, 21(3), 480-495. [CrossRef]
  • 16. Auiewiriyanukul, W., Saburi, W., Kato, K., Yao, M., Mori, H. (2018). Function and structure of GH13_31 α-glucosidase with high α-(1→4)-glucosidic linkage specificity and transglucosylation activity. FEBS Letters, 592(13), 2268-2281. [CrossRef]
  • 17. Trott, O., Olson, A.J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. Journal of Computational Chemistry, 31(2), 455. [CrossRef]
  • 18. Arslan, G., Gökçe, B., Muhammed, M.T., Albayrak, Ö. (2023). Synthesis, DFT calculations, and molecular docking study of acetohydrazide-based sulfonamide derivatives as paraoxonase 1 inhibitors. ChemistrySelect, 8(10), e202204630. [CrossRef]
  • 19. Muhammed, M.T., Kökbudak Z., Akkoç S. (2023). Cytotoxic activities of the pyrimidine-based acetamide and isophthalimide derivatives: An in vitro and in silico studies. Molecular Simulation, 49(10), 982-992. [CrossRef]
  • 20. Gökçe, B., Muhammed, M.T. (2023). Evaluation of in vitro effect, molecular docking, and molecular dynamics simulations of some dihydropyridine-class calcium channel blockers on human serum paraoxonase 1 (hPON1) enzyme activity. Biotechnology and Applied Biochemistry, 70(5), 1707-1719. [CrossRef]
  • 21. Akman, S., Akkoc, S., Zeyrek, C.T., Muhammed, M.T., Ilhan, I.O. (2023). Density functional modeling, and molecular docking with SARS-CoV-2 spike protein (Wuhan) and omicron S protein (variant ) studies of new heterocyclic compounds including a pyrazoline nucleus. Journal of Biomolecular Structure and Dynamics, 41(22), 12951-12965. [CrossRef]
  • 22. Maity, D., Singh, D., Bandhu, A. (2023). Mce1R of Mycobacterium tuberculosis prefers long‑chain fatty acids as specific ligands: A computational study. Molecular Diversity, 27, 2523-2543. [CrossRef]

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri (Diğer)
Bölüm Araştırma Makalesi
Yazarlar

Muhammed Tilahun MUHAMMED 0000-0003-0050-5271

Nesli AKSOY Bu kişi benim 0009-0000-2781-2162

Aybüke KRILMAZ Bu kişi benim 0009-0000-3847-041X

Enise TÜRKMEN Bu kişi benim 0009-0004-2259-971X

Erken Görünüm Tarihi 5 Ocak 2024
Yayımlanma Tarihi 20 Ocak 2024
Gönderilme Tarihi 10 Eylül 2023
Kabul Tarihi 21 Aralık 2023
Yayımlandığı Sayı Yıl 2024 Cilt: 48 Sayı: 1

Kaynak Göster

APA MUHAMMED, M. T., AKSOY, N., KRILMAZ, A., TÜRKMEN, E. (2024). TOWARDS UNDERSTANDING NATURAL ALPHA-GLUCOSIDASE INHIBITORS: A COMPUTATIONAL STUDY. Journal of Faculty of Pharmacy of Ankara University, 48(1), 205-214. https://doi.org/10.33483/jfpau.1356028
AMA MUHAMMED MT, AKSOY N, KRILMAZ A, TÜRKMEN E. TOWARDS UNDERSTANDING NATURAL ALPHA-GLUCOSIDASE INHIBITORS: A COMPUTATIONAL STUDY. Ankara Ecz. Fak. Derg. Ocak 2024;48(1):205-214. doi:10.33483/jfpau.1356028
Chicago MUHAMMED, Muhammed Tilahun, Nesli AKSOY, Aybüke KRILMAZ, ve Enise TÜRKMEN. “TOWARDS UNDERSTANDING NATURAL ALPHA-GLUCOSIDASE INHIBITORS: A COMPUTATIONAL STUDY”. Journal of Faculty of Pharmacy of Ankara University 48, sy. 1 (Ocak 2024): 205-14. https://doi.org/10.33483/jfpau.1356028.
EndNote MUHAMMED MT, AKSOY N, KRILMAZ A, TÜRKMEN E (01 Ocak 2024) TOWARDS UNDERSTANDING NATURAL ALPHA-GLUCOSIDASE INHIBITORS: A COMPUTATIONAL STUDY. Journal of Faculty of Pharmacy of Ankara University 48 1 205–214.
IEEE M. T. MUHAMMED, N. AKSOY, A. KRILMAZ, ve E. TÜRKMEN, “TOWARDS UNDERSTANDING NATURAL ALPHA-GLUCOSIDASE INHIBITORS: A COMPUTATIONAL STUDY”, Ankara Ecz. Fak. Derg., c. 48, sy. 1, ss. 205–214, 2024, doi: 10.33483/jfpau.1356028.
ISNAD MUHAMMED, Muhammed Tilahun vd. “TOWARDS UNDERSTANDING NATURAL ALPHA-GLUCOSIDASE INHIBITORS: A COMPUTATIONAL STUDY”. Journal of Faculty of Pharmacy of Ankara University 48/1 (Ocak 2024), 205-214. https://doi.org/10.33483/jfpau.1356028.
JAMA MUHAMMED MT, AKSOY N, KRILMAZ A, TÜRKMEN E. TOWARDS UNDERSTANDING NATURAL ALPHA-GLUCOSIDASE INHIBITORS: A COMPUTATIONAL STUDY. Ankara Ecz. Fak. Derg. 2024;48:205–214.
MLA MUHAMMED, Muhammed Tilahun vd. “TOWARDS UNDERSTANDING NATURAL ALPHA-GLUCOSIDASE INHIBITORS: A COMPUTATIONAL STUDY”. Journal of Faculty of Pharmacy of Ankara University, c. 48, sy. 1, 2024, ss. 205-14, doi:10.33483/jfpau.1356028.
Vancouver MUHAMMED MT, AKSOY N, KRILMAZ A, TÜRKMEN E. TOWARDS UNDERSTANDING NATURAL ALPHA-GLUCOSIDASE INHIBITORS: A COMPUTATIONAL STUDY. Ankara Ecz. Fak. Derg. 2024;48(1):205-14.

Kapsam ve Amaç

Ankara Üniversitesi Eczacılık Fakültesi Dergisi, açık erişim, hakemli bir dergi olup Türkçe veya İngilizce olarak farmasötik bilimler alanındaki önemli gelişmeleri içeren orijinal araştırmalar, derlemeler ve kısa bildiriler için uluslararası bir yayım ortamıdır. Bilimsel toplantılarda sunulan bildiriler supleman özel sayısı olarak dergide yayımlanabilir. Ayrıca, tüm farmasötik alandaki gelecek ve önceki ulusal ve uluslararası bilimsel toplantılar ile sosyal aktiviteleri içerir.