MOLECULAR DOCKING AND GRAPHICAL TRAJECTORY ANALYSIS OF CINNAMOMUM ZEYLANICUM COMPOUNDS FOR TARGETING HUMAN MALTASE-GLUCOAMYLASE IN DIABETES MANAGEMENT

VYSHNAVI VISHWANADHAM RAO; KOPPALA NARAYANAPPA SHANTI; DINESH SOSALAGERE MANJEGOWDA

doi:10.22159/ijap.2025v17i6.55175

Authors

VYSHNAVI VISHWANADHAM RAO Department of Chemistry, MES College of Arts, Science and Commerce, Bengaluru-560003, India. Department of Biotechnology, PES University, Bengaluru-560085, India https://orcid.org/0009-0006-2769-0963
KOPPALA NARAYANAPPA SHANTI Department of Biotechnology, PES University, Bengaluru-560085, India
DINESH SOSALAGERE MANJEGOWDA Department of Human Genetics, School of Basic and Applied Sciences, Dayananda Sagar University, Bengaluru-560078, Karnataka, India https://orcid.org/0000-0001-8915-3983

DOI:

https://doi.org/10.22159/ijap.2025v17i6.55175

Keywords:

Alpha-cadinol, Cinnamomum zeylanicum, Diabetes management, In silico, Maltase-glucoamylase inhibition, Molecular dynamics, Molecular docking, Phytocompounds

Abstract

Objective: Maltase-glucoamylase is an essential enzyme involved in the final hydrolysis of dietary carbohydrates into glucose, facilitating postprandial glucose absorption. Its heightened activity exacerbates glucose spikes, a hallmark of type 2 diabetes, making it a pivotal target for therapeutic intervention. This research aims to explore the inhibitory potential of phytocompounds from Cinnamomum zeylanicum as promising enzyme inhibitors, with acarbose serving as a reference standard.

Methods: Eighteen phytocompounds were screened via molecular docking and molecular dynamics (MD) simulations. Binding affinity, residue interactions, and structural stability were assessed, alongside pharmacokinetic and toxicity profiling using absorption, distribution, metabolism, excretion, and toxicity (ADMET) tools.

Results: Alpha-cadinol and cis-4-Benzyl-2,6-diphenyltetrahydropyran emerged as top candidates with binding energies of-10.21 and-10.17 kcal/mol, respectively, surpassing acarbose (-9.11 kcal/mol). Interaction analysis revealed that alpha-cadinol formed hydrogen bonds with TYR A: 1251 and GLY A: 1588, while cis-4-Benzyl-2,6-diphenyltetrahydropyran engaged residues such as HIS A: 1710 and THR A: 1699 through a combination of hydrogen bonding and aromatic interactions. Molecular dynamics simulations confirmed the stability of these complexes, with root mean square deviation values of 0.33 nm for alpha-cadinol and 0.34 nm for cis-4-Benzyl-2,6-diphenyltetrahydropyran, comparable to acarbose. Reductions in solvent accessibility and root mean square fluctuation further demonstrated the stabilising effects of these compounds on the enzyme. Pharmacokinetic profiling revealed favourable absorption and bioavailability for both compounds, suggesting their suitability as oral therapeutics.

Conclusion: These findings highlight alpha-cadinol and cis-4-Benzyl-2,6-diphenyltetrahydropyran as potential alternatives to acarbose with possibly improved safety and efficacy profiles. However, in vitro and in vivo validation is necessary to confirm their therapeutic applicability and establish their metabolic stability. This study offers a significant step toward developing novel enzyme inhibitors for effective diabetes management and paves the way for future experimental and clinical exploration.

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