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Comprehensive Computational Studies of Naturally Occurring Kuguacins as Antidiabetic Agents by Targeting Visfatin

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Abstract

Diabetes mellitus continues to be a major health concern for the global population. Targeting visfatin has been identified as a possible channel to manage the disease effectively. Kuguacins are triterpenoids with established antidiabetic activity. Therefore, this study examines the visfatin activating potentials of kuguacins using molecular docking, density functional theory (DFT), molecular dynamics (MD) simulation, ADMET and drug-likeness methods. The DFT studies employed B3LYP/6+3G (d, p) basis set to calculate the electronic parameters while MD simulation was performed for 100 ns. ADMET online server was used to determine their drug-likeness and pharmacokinetic properties. Kuguacin I (−11.3 kcal/mol), kuguacin F (−10.8 kcal/mol), kuguacin R (−10.8 kcal/mol) and kuguacin M (−10.2 kcal/mol) were identified as the top-ranked molecules. The quantum chemical properties of the hit molecules suggest them as suitable visfatin activators. The RMSD and RMSF plots showed that the top-ranked kuguacins were stable and suitable as visfatin activators. Also, the MMGBSA binding free energy of the ligands ranged between −43.99 kcal/mol and −34.94 kcal/mol. The ADMET and drug-likeness properties reveal the top-ranked molecules as suitable drug candidates. The findings from this study can be verified in vitro and in vivo.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Obafemi Awolowo University, Ile-Ife, Nigeria

    Samson O. Famuyiwa, Emmanuel G. Fakola & Kolade O. Faloye

  2. Department of Computer Science, Jamia Millia Islamia, New Delhi, India

    Shaban Ahmad & Khalid Raza

  3. Department of Pharmacology, Faculty of Pharmacy, Federal University of Oye-Ekiti, Oye-Ekiti, Nigeria

    Ayobami J. Olusola

  4. Department of Pharmacognosy, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria

    Stephen A. Adesida

  5. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria

    Faith O. Obagunle

  6. Department of Chemistry, School of Science, Federal College of Education, Okene, Nigeria

    Jeremiah P. Ugwo

  7. Department of Biochemistry, Faculty of Science, Obafemi Awolowo University, Ile-Ife, Nigeria

    Esther I. Oyelekan

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  1. Samson O. Famuyiwa
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  2. Shaban Ahmad
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Contributions

SOF: Conceptualisation and supervision. SA and KR: Methodology, formal analysis, review and editing. EGF: investigation, original draft preparation, review and editing. AJO: Methodology and formal analysis. SAA: Methodology and original draft preparation. FOO: formal analysis, review and editing. Khalid Raza: Supervision, review and editing. JPU: Methodology and formal analysis. EIO: Formal analysis and original draft preparation. KOF: Conceptualisation, supervision, methodology, original draft preparation, review and editing. All authors read and approved the final manuscript.

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Correspondence to Kolade O. Faloye.

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Famuyiwa, S.O., Ahmad, S., Fakola, E.G. et al. Comprehensive Computational Studies of Naturally Occurring Kuguacins as Antidiabetic Agents by Targeting Visfatin. Chemistry Africa 6, 1415–1427 (2023). https://doi.org/10.1007/s42250-023-00604-8

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