Diabetes mellitus is a group of metabolic disorders characterised by chronic hyperglycemia resulting either
from a deficiency of insulin, or decreased ability to transduce the insulin signal, or both. Insulin resistance and β-cell dysfunction
are two fundamental defects known to precede the onset of type 2 diabetes. PTP 1B is considered to function as a
negative regulator of insulin signal transduction by dephosphorylating phosphotyrosine residues. 2,4-Thiazolidinediones
(TZDs) have long been considered as antihyperglycemic agents which act by ameliorating insulin resistance and thereby
normalizing elevated blood glucose level. A three dimensional quantitative structure-activity relationship (3D-QSAR)
study was performed on a novel class of thiazolidinedione derivatives using self-organizing molecular field analysis
(SOMFA) to correlate their molecular architecture with observed PTP 1B inhibitory activities. The master grid maps derived
from the best model were used to display the contribution of both electrostatic and shape potential that can be
mapped back onto structural features relating to the trends in inhibitory activities. The present SOMFA study indicated the
indispensable molecular features which can be further explored for structural modifications of these lead molecules in order
to optimize PTP 1B inhibitory activity.
Keywords: Diabetes, Insulin, PTP 1B, SOMFA, Thiazolidinedione, 3D-QSAR.
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