brhejoThe BRICS Health JournalThe BRICS Health Journal3034-47003034-4719Sechenov University10.47093/3034-4700.2025.2.1.53-68brhejo-23Research ArticleСтатьиMulti-targeted molecular docking, pharmacokinetic analysis, and drug-likeness evaluation of alkaloids for anti-diabetic drug developmentMeressaA.

Asfaw Meressa, MSc, Researcher, Traditional and Modern Medicine Research and Development Directorate, In silico and Modern Medicine Research Division

P. O. Box 1005, Addis Ababa, Ethiopia

asfawmeresa03@gmail.comhttps://orcid.org/0000-0002-0235-4158GirmaB.

Biruktawit Girma, MSc, Researcher, Traditional and Modern Medicine Research and Development In silico and Modern Medicine Research Division 

P. O. Box 1005, Addis Ababa, Ethiopia

https://orcid.org/0009-0005-3755-188XNegassaT.

Temesgen Negassa, MSc, Researcher, Traditional and Modern Medicine Research and Development In silico and Modern Medicine Research Division

P. O. Box 1005, Addis Ababa, Ethiopia

https://orcid.org/0000-0002-7758-6367NigussieG.

Gashaw Nigussie, MSc, Associate researcher, Traditional and Modern Medicine Research and De- velopment In silico and Modern Medicine Research Division; Communicable and Non-Communicable Research In silico and Modern Medicine Research Division

P. O. Box 1005, Addis Ababa, Ethiopia

https://orcid.org/0009-0008-1718-050XKasahunM.

Mewded Kasahun, MSc, Researcher, Traditional and Modern Medicine Research and Development In silico and Modern Medicine Research Division

https://orcid.org/0009-0000-2123-3960AbdisaN.

Negessa Abdisa, MSc, Researcher, Traditional and Modern Medicine Research and Development In silico and Modern Medicine Research Division

P. O. Box 1005, Addis Ababa, Ethiopia

https://orcid.org/0000-0002-5924-4005AshenefS.

Sintayehu Ashenef, MSc, Associate researcher, Traditional and Modern Medicine Research and Development In silico and Modern Medicine Research Division

P. O. Box 1005, Addis Ababa, Ethiopia

https://orcid.org/0000-0003-4108-0484TayeS.

Samson Taye, MSc, Researcher, Communicable and Non-Communicable Research In silico and Modern Medicine Research Division

P. O. Box 1005, Addis Ababa, Ethiopia

https://orcid.org/0009-0002-8809-9780BelitiboD. B.

Dereilo Bekere Belitibo, MSc, Lecturer, Associate researcher, Traditional and Modern Medicine Research and Development In silico and Modern Medicine Research Division

P. O. Box 1005, Addis Ababa, Ethiopia

https://orcid.org/0000-0001-9270-5558AnimawZ.

Zelalem Animaw, PhD, Assistant professor, Researcher, Department of Biomedical Sciences, College of Health Sciences, Debre Tabor University; Traditional and Modern Medicine Research and Development In silico and Modern Medicine Research Division, Armauer Hansen Research Institute (AHRI),

P. O. Box 272, Debre Tabor, Ethiopia; P. O. Box 1005, Addis Ababa, Ethiopia

https://orcid.org/0000-0002-1100-5718WakeneW.

Wakuma Wakene, MSc, Lecturer, Associate researcher, Traditional and Modern Medicine Research and Development In silico and Modern Medicine Research Division

P. O. Box 1005, Addis Ababa, Ethiopia

https://orcid.org/0009-0003-2557-5353AkeleB.

Baye Akele, MSc, Assistant professor, Associate researcher, Traditional and Modern Medicine Research and Development In silico and Modern Medicine Research Division

P. O. Box 1005, Addis Ababa, Ethiopia

https://orcid.org/0000-0002-5301-9923EndaleM.

Milkyas Endale, PhD, Professor, Lead researcher, Traditional and Modern Medicine Research and Development Directorate, In silico and Modern Medicine Research Division

P. O. Box 1005, Addis Ababa, Ethiopia

Armauer Hansen Research InstituteEthiopiaDebre Tabor University; Armauer Hansen Research InstituteEthiopia202520052025215368Copyright © Meressa A., Girma B., Negassa T., Nigussie G., Kasahun M., Abdisa N., Ashenef S., Taye S., Belitibo D.B., Animaw Z., Wakene W., Akele B., Endale M., 20252025Meressa A., Girma B., Negassa T., Nigussie G., Kasahun M., Abdisa N., Ashenef S., Taye S., Belitibo D.B., Animaw Z., Wakene W., Akele B., Endale M.Meressa A., Girma B., Negassa T., Nigussie G., Kasahun M., Abdisa N., Ashenef S., Taye S., Belitibo D.B., Animaw Z., Wakene W., Akele B., Endale M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.bricshealthjournal.com/jour/article/view/23

Diabetes mellitus is a global health challenge, particularly in low-income regions, leading to severe complications. Plant-derived alkaloids offer potential as alternatives to conventional therapies. This study evaluated 31 alkaloids for antidiabetic drug development through molecular docking, pharmacokinetics, and drug-likeness analyses. Four standard drugs (epalrestat, metformin, acarbose, glibenclamide) and four targets (aldose reductase, adenosine monophosphate-activated protein kinase, α-glucosidase, protein tyrosine phosphatase 1B) were used for computational simulations. 

Molecular docking revealed that alkaloids mahanimbine (-11.5 kcal/mol), echinulin (11.3 kcal/mol), coptisine (-10.9 kcal/mol), and groenlandicine  (-9.7 kcal/mol) have substantial binding affinities against aldose reductase compared to epalrestat (-9.3 Kcal/mol).  In contrast to metformin  (-4.8 kcal/mol), coptisine, echinulin, sanguinarine, and groelandicine showed superior binding affinities against adenosine monophosphateactivated protein kinase.  In comparison to acarbose (-8.4 Kcal/mol), coptisine (-9.7 Kcal/mol), sanguinarine (-9.3 Kcal/mol), mahanimbine (-8.9 Kcal/mol), and echinulin (-8.9 Kcal/mol) demonstrated better docking scores against α-glucosidase. Jatrorrhizine, coptisine, sanguinarine, mahanimbine and echinuline respectively demonstrated higher binding scores of 8.8, -7.5, -7.5 and -7.2 Kcal/mol against protein tyrosine phosphatase 1B than glibenclamide (-7.0 Kcal/mol). Most alkaloids adhered to Lipinski’s rule, except casuarine 6-O-α-glucoside and conophylline. Pharmacokinetics identified pinoline as highly bioavailable and central nervous system penetrant, while conophylline had poor bioavailability.

The study concluded that alkaloids including mahanimbine, echinulin, coptisine, groenlandicine, sanguinarine, and jatrorrhizine show strong binding affinities and favorable pharmacokinetic properties, requiring further in vitro and in vivo studies for therapeutic validation.

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The authors declare that there are no conflicts of interest present.