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Molecular similarity analysis on biologically active macrocyclic bis(bibenzyls)
1Department of Chemical Information Technology, Technical University of Budapest, Hungary.
Journal of Molecular Recognition : JMR
|March 1, 1996
Summary
Conformational analysis of marchantin A and riccardin A revealed differences in their molecular structures. These differences in steric and electrostatic properties explain riccardin A
Area of Science:
- Natural Product Chemistry
- Computational Chemistry
- Molecular Pharmacology
Background:
- Marchantin A and riccardin A are macrocyclic bis(bibenzyl) compounds with potential biological activities.
- Understanding their conformational properties is crucial for elucidating their mechanism of action.
Purpose of the Study:
- To perform a detailed conformational analysis of marchantin A and riccardin A.
- To investigate the molecular mobility of their macrocyclic rings.
- To correlate their complexation properties with calmodulin inhibitor activity.
Main Methods:
- Systematic Unbounded Multiple Minimum (SUMM) search for conformational analysis.
- Variable temperature 1H-NMR spectroscopy to study macrocyclic ring mobility.
- Molecular similarity analysis of minimum energy conformers, evaluating steric, electrostatic, and hydrophobic properties.
Main Results:
- Identified distinct minimum energy conformers for marchantin A and riccardin A.
- Demonstrated differences in the steric and electrostatic profiles between the two compounds.
- Established a correlation between complexation properties and calmodulin inhibitory activity.
Conclusions:
- The observed differences in steric and electrostatic profiles between marchantin A and riccardin A are likely responsible for riccardin A's reduced Ca2+ affinity and calmodulin inhibitory activity.
- This study provides insights into the structure-activity relationships of these natural products.