EXPLORING NEW MONOAMINO OXIDASE- A (MAO-A) SELECTIVE INHIBITORS FROM CUCURBITO PEPO: A VIRTUAL SCREENING, MOLECULAR DOCKING, MD SIMULATIONS AND ADMET ANALYSIS

MAHENDRA GOWDRU SRINIVASA; SUDEEP D GHATE; R. SHYAMA PRASAD RAO; MANOHAR MAHADEV

doi:10.22159/ijap.2025v17i1.52084

Authors

MAHENDRA GOWDRU SRINIVASA Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Department of Pharmaceutical Chemistry, Mangalore-575018, Karnataka, India https://orcid.org/0000-0001-6105-7025
SUDEEP D GHATE Nitte (Deemed to be University), Center for Bioinformatics, Mangaluru-575018, Karnataka, India
R. SHYAMA PRASAD RAO Nitte (Deemed to be University), Center for Bioinformatics, Mangaluru-575018, Karnataka, India https://orcid.org/0000-0002-2285-6788
MANOHAR MAHADEV Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Department of Pharmaceutics Mangalore-575018, Karnataka, India

DOI:

https://doi.org/10.22159/ijap.2025v17i1.52084

Keywords:

Antidepressant, Curcubito pepo, Docking, MAO-A

Abstract

Objective: This study aimed to identify potential Monoamine oxidase (MAO) inhibitors from Cucurbita pepo to address the increasing prevalence of neurological and neuropsychiatric disorders, such as stroke, Alzheimer's, Parkinson's, autism, migraines, and depression, by targeting key enzymes involved in neurotransmitter degradation.

Methods: The study utilised molecular docking and pharmacological, physiological, and ADMET property analyses to screen compounds from Cucurbita pepo. Ten promising MAO inhibitors were shortlisted for further analysis. Extensive Molecular Dynamics (MD) simulations were conducted over 100 nanoseconds to assess the stability and dynamic behaviour within the MAO-A complex.

Results: Based on molecular docking results, four shortlisted compounds were identified as potential MAO-A inhibitors. Atomic-level docking studies were used to explore the binding mechanisms of the phytoconstituents within the active site of the MAO-A enzyme. The binding free energies of these compounds ranged from -9.183 to -6.001 kcal/mol. Phytoconstituent Compound C1 had the highest binding affinity with a G score of -9.183 kcal/mol, followed by Compound C2 with a G score of -9.045 kcal/mol. MD simulations further confirmed that both C1 and C2 formed highly stable complexes with MAO-A, suggesting their potential as effective inhibitors.

Conclusion: Compounds C1 and C2 from Cucurbita pepo show promise as stable and effective MAO-A inhibitors. Further experimental validation is required to confirm these findings and evaluate their therapeutic potential in treating neurological disorders.

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