What question did this study set out to answer?

To rationally design and discover novel indole-linked guanidine derivatives as selective BACE-1 inhibitors for the treatment of Alzheimer's disease.

August 16, 2026Journal of Computational Biophysics and Chemistry

Integrated Computational Design and Discovery of Novel Indole-Linked Guanidine Derivatives as BACE-1 Inhibitors for Alzheimer's Disease

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Authors

PGPitam GhoshIndo Soviet Friendship College of Pharmacy RDRyena DhirIndo Soviet Friendship College of Pharmacy DSDinki SharmaIndo Soviet Friendship College of Pharmacy

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Implication

Computational study identifies novel indole-linked guanidine derivatives targeting BACE-1, suggesting compound R2 as a potential disease-modifying lead for Alzheimer's disease.

Key Points

To rationally design and discover novel indole-linked guanidine derivatives as selective BACE-1 inhibitors for the treatment of Alzheimer's disease.
Conducted integrated computational workflows including pharmacophore modeling, atom- and field-based 3D-QSAR modeling, and ligand-protein docking (PDB ID: 4DJU).
Performed R-group enumeration to generate 2,408 derivatives, followed by pharmacophore-guided virtual screening against ZINC databases, ADME profiling, and MD simulations.
Established atom-based (R²=0.9386, Q²=0.7432) and field-based (R²=0.8492, Q²=0.6644) 3D-QSAR models from the top pharmacophore hypothesis DDHRR_1 (survival score: 5.7767).
Identified enumerated derivatives R1 and R2 with high binding affinities of -10.339 kcal/mol and -9.611 kcal/mol, compared to parent dataset compound B38 (-6.567 kcal/mol).
Identified derivative R2 as the top lead compound over screened ZINC candidates, highlighting the need for subsequent synthesis and blood-brain barrier permeability evaluations.

Cite This Study

Ghosh et al. (2026) studied this question.

synapsesocial.com/papers/6a817a01f2fb91fc834ad918 https://doi.org/10.1142/s2737416526501152

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Implication

Computational study identifies novel indole-linked guanidine derivatives targeting BACE-1, suggesting compound R2 as a potential disease-modifying lead for Alzheimer's disease.

Integrated Computational Design and Discovery of Novel Indole-Linked Guanidine Derivatives as BACE-1 Inhibitors for Alzheimer's Disease

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Implication

Key Points

Cite This Study

Integrated Computational Design and Discovery of Novel Indole-Linked Guanidine Derivatives as BACE-1 Inhibitors for Alzheimer's Disease

Discussion

Member takes

Implication

Key Points

Cite This Study

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