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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. October 2006, Volume 5, Number 10, 503-514 |
Pharmacophore Mapping of Tricyclic Isoxazoles for Their Affinity Towards Alpha-2 Adrenoreceptors
Soma Samanta, Sk. Mahasin Alam, Parthasarathi Panda, and Tarun Jha
Internet Electron. J. Mol. Des. 2006, 5, 503-514
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Abstract:
Blockage of alpha-2 adrenoreceptors in brain enhances noradrenergic
neurotransmission and increases extracellular dopamine as well as
serotonin (5-HT) levels, which is beneficial for depressant patients. To
identify pharmacophoric requirements, a quantitative structure activity
relationship (QSAR) study was performed using electrotopological
state atom (ETSA) indices and refractotopological state atom (RTSA)
indices on tricyclic isoxazole derivatives for their affinity towards the
alpha-2 adrenoreceptors. Correlation analysis and multiple linear
regression analysis were employed to model the experimental activity.
The QSAR models were obtained separately for alpha-2A and 2C
adrenoreceptor binding affinity. It was found that some atoms played
important roles to both the activities and some other atoms played
different roles in selectivity of compound towards alpha-2A and 2C
adrenoreceptor binding affinity. Electrotopological state atom (ETSA)
and refractotopological state atom (RTSA) indices have potentiality to
determine or recognize the pharmacophoric atoms and combination of
these two helps to map pharmacophore of trycyclic isoxazoles.
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