MOLECULAR DOCKING STUDIES OF ISATIN-LINKED CHALCONE DERIVATIVES AS PANKASSOCIATED NEURODEGENERATIVE DRUG CANDIDATES AND THEIR ADMET PREDICTION

MARAPATLA SHINY; GIRIJA SASTRY VEDULA; KUSUME SIREESHA; GARA SUREKHA; CHALLA VIJAYA SRUTHI

doi:10.22159/ajpcr.2025v18i5.54257

Authors

MARAPATLA SHINY Department of Pharmaceutical Chemistry, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh, India.
GIRIJA SASTRY VEDULA Department of Pharmaceutical Chemistry, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh, India.
KUSUME SIREESHA Department of Pharmaceutical Chemistry, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh, India.
GARA SUREKHA Department of Pharmaceutical Chemistry, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh, India.
CHALLA VIJAYA SRUTHI Department of Pharmaceutical Chemistry, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, Andhra Pradesh, India.

DOI:

https://doi.org/10.22159/ajpcr.2025v18i5.54257

Keywords:

Isatin-linked chalcones, PanK-associated neurodegeneration, Molecular docking, Pantazine-PZ-2891, ADMET prediction, Structureactivity relationship

Abstract

Objective: Molecular docking studies were carried out on fifteen novel Isatin-linked chalcone derivatives to evaluate their potential as drug candidates for PanK-associated neurodegeneration.

Methods: The compounds were computationally analyzed using Molegro Virtual Docker, Autodocktools, and AU docker against the Pantothenate kinase protein (PDB ID: 6B3V).

Results: The molecular docking analysis revealed that the synthesized chalcones exhibited significant binding affinities with dock scores ranging from −8.4 to −9.1 kcal/mol, surpassing the standard Pantazine derivative PZ-2891 (−7.0 kcal/mol). Compound 14 demonstrated superior binding affinity (−9.1 kcal/mol) through key interactions with SER-175, PHE-306, ASN-305, and THR-11 residues. The binding modes were validated through consensus scoring and root-mean-square deviation analysis. ADMET predictions using SwissADME indicated favorable drug-like properties for the compounds, including blood-brain barrier permeability and acceptable bioavailability scores.

Conclusion: The computational analysis revealed that 80% of the compounds exhibited interactions with serine residues, similar to the standard drug’s binding pattern. Structure-activity relationship analysis identified key pharmacophoric features contributing to enhanced binding affinity, particularly the presence of specific substituents on the chalcone scaffold.

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