Exploring the pKa, Molecular Binding, and Caspase-3 Activation Potential of Coumarin Derivatives

Q: How can I download an article?

To download an article from SID, first log in to the site, search for the article title, and click on the 'Download Article' option.

Q: How can I download an ISI article?

To download an ISI article on SID, enter the keyword or article title in the search bar, view the relevant results, click on the desired article, and select the 'Download Article' option.

Q: How can I access the SID database?

To access the SID database, visit SID.ir, create an account, and log in to access scientific resources.

Q: Is downloading articles from SID free?

Some articles on SID are available for free, while others require payment. Details are specified on the article's page.

Altunterim Erkan Semra; Erdag Emine; Alsaloumi Louai; Celik Hayati

مرکز اطلاعات علمی Scientific Information Database (SID) - Trusted Source for Research and Academic Resources

Journal Paper

Paper Information

Journal: Iranian Journal of Chemistry and Chemical Engineering Year:2025 | Volume:44 | Issue:10 Page(s): 2630-2641

Download Full-Text

View:

Download:

Cites:

Information Journal Paper

Title

Exploring the pKa, Molecular Binding, and Caspase-3 Activation Potential of Coumarin Derivatives

Author(s)

Altunterim Erkan Semra | Erdag Emine | Alsaloumi Louai | Celik Hayati | Issue Writer Certificate

Keywords

Coumarin derivatives

pKa

Caspase-3

Apoptosis

Molecular Docking

Molecular Dynamics Simulations

Abstract

Caspase-3 is a central executioner protease in Apoptosis, and its activation by small molecules is considered a promising anticancer strategy. Coumarin derivatives are known for their diverse biological activities, but the influence of structural modifications, particularly hydroxyl group positioning, on acidity constants (pKa) and binding affinity to Caspase-3 remains underexplored. This study aimed to investigate how the electronic and spatial configuration of hydroxyl substituents in Coumarin derivatives modulates their pKa behavior and binding potential to Caspase-3, with the ultimate goal of identifying promising scaffolds for Caspase-3 activation. A series of twenty-one structurally diverse Coumarin derivatives was analyzed. pKa values were determined experimentally by UV–Vis spectrophotometry and theoretically predicted using MarvinSketch software. Molecular Docking (AutoDock) and Molecular Dynamics Simulations (GROMACS) were conducted, followed by MM/PBSA binding free energy calculations to evaluate interactions with Caspase-3 (PDB ID: 3DEI). Experimental and theoretical pKa₁ values exhibited strong concordance (R² = 0.93), while discrepancies were observed in pKa₂ values, especially among piperazine- and piperidine-substituted derivatives. Molecular Docking identified Compound 13 as the most potent derivative (ΔGbinding = –9.3 kcal/mol), with its 7-position hydroxyl group forming strong hydrogen bonds and electrostatic interactions particularly with Arg207 and His121. In contrast, derivatives with the hydroxyl at position 6 showed weakened interactions and reduced affinity. The position-dependent ionization states significantly influenced the molecular interaction profiles. Conclusion: These findings provide mechanistic insight into how small changes in hydroxyl positioning affect ionization and Caspase-3 binding, offering valuable guidance for pKa-optimized design of novel small-molecule Caspase-3 activators with potential anticancer applications.

Multimedia

No record.

Cites

No record.

References

No record.

Cite

Related Journal Papers

No record.

Related Seminar Papers

No record.

Related Plans