Structure-activity study on anticonvulsant (thio) hydantoins using molecular connectivity indices

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Pharmacology

Background:

• Hydantoin and thiohydantoin analogs are explored for anticonvulsant properties.
• Quantitative Structure-Activity Relationships (QSAR) are crucial for drug design.
• Molecular connectivity indices offer a way to quantify molecular structure.

Purpose of the Study:

• To investigate the correlation between molecular connectivity indices and anticonvulsant activity.
• To identify active ranges for molecular connectivity and valence molecular connectivity indices.
• To assess the predictive accuracy of these topological descriptors for anticonvulsant effects.

Main Methods:

• Computation of molecular connectivity index and valence molecular connectivity index for 82 hydantoin/thiohydantoin analogs.
• Identification of specific ranges of these indices associated with anticonvulsant activity.
• Comparison of predicted activity based on indices with experimentally reported activity against maximal electroshock convulsions.

Main Results:

• A strong relationship was found between molecular connectivity indices and anticonvulsant activity.
• Specific active ranges for molecular connectivity and valence molecular connectivity indices were determined.
• The computed indices demonstrated a high degree of accuracy in predicting anticonvulsant activity.

Conclusions:

• Molecular connectivity indices are effective topological descriptors for predicting anticonvulsant activity.
• The identified active ranges can guide the design of novel anticonvulsant hydantoin analogs.
• This QSAR approach offers a valuable tool for accelerating drug discovery in epilepsy treatment.