On Application of Carhart Atom Pairs to Predict Anticonvulsant Activity
Journal Title: American Journal of Biochemistry and Biotechnology - Year 2006, Vol 2, Issue 3
Abstract
About 50 million people in the world suffer from epilepsy, especially in childhood, adolescence and old age. Available treatment fails to control epilepsy in up to 30% of affected people. In developing countries, however, the amount of patients that do not receive adequate treatment climbs up to 75%. Moreover, the new generation of antiepileptic drugs (AEDs) causes important central and peripheral side effects, including ataxia, diplopia, dizziness, headache, nausea, allergies and sedation. A mathematical model previously developed by Bagchi and Maiti, involving Carhart atom pairs and similarity measures, is applied in the prediction of anticonvulsant activity of two sets of compounds which have shown to be active in the Maximal Electroshock Seizure (MES) test, meaning that their mechanism of action can be at least partially explained through sodium channels blockade. Nine structurally heterogeneous molecules define the first set of compounds, with Carhart similarities to carbamazepine ranging from 0.005 to 0.593. The second set is defined by four benzodiazepines derivatives with Carhart similarities to THIQ-10c ranging from 0.533 to 0.570. A new, more specific, model is constructed based on the one from Bagchi and Maiti and a pharmacophore previously identified in our laboratory through an active analog approach. Applied to both sets of compounds, our model shows smaller average percentage error and average absolute error in the prediction than the one form Bagchi and Maiti and smaller SD as well. Accuracy and precision in the prediction also increases compared to those obtained when using bare similarity coefficients as relative activity indicators.
Authors and Affiliations
Alan Talevi
Keywords
Related Articles
- EP ID EP91186
- DOI -
- Views 98
- Downloads 0
Bioceramics for Tissue Engineering Applications – A Review
Three dimensional (3-D) scaffolds have been explored in an attempt to persuade the body to heal or repair tissues that do not do so spontaneously. Considerable advances in tissue engineering and regeneration have been...
Nanoceramic Matrices: Biomedical Applications
Natural bone consisted of calcium phosphate with nanometer-sized needle-like crystals of approximately 5-20 nm width by 60 nm length. Synthetic calcium phosphates and Bioglass are biocompatible and bioactive as they bo...
Effective Thermophilic Composting of Crop Residues for Inactivation of Tobacco Mosaic Virus
An effective thermophilic composting bioreactor, in which a homogenous distribution of temperature was maintained at 63-65°C by the addition of a bioavailable carbon and low mixing, was developed. The bioreactor operat...
Mapping QTLs Linked to Physio-Morphological and Plant Production Traits under Mapping QTLs Linked to Physio-Morphological and Plant Production Traits under
Drought stress is a major constraint for rice (Oryza sativa L.) production and yield stability in rainfed ecosystems. Identifying genomic regions (QTLs) contributing in drought resistance will help to develop rice cult...
The Biology of p21 Waf1/Cip1 - Review Paper
p21 WAF1/Cip1 belongs to the Cip/Kip family of cyclin kinase inhibitors (CKI) (p21 Waf1/Cip1 , p27 Kip1 , p57 Kip1 ). p21 Waf1/Cip1 was first described as a potent and universal inhibitor of cyclin-dependent kinases (C...