Sulphonamides as inhibitors of protein tyrosine phosphatase 1B: A three-dimensional quantitative structure-activity relationship study using self-organizing molecular field analysis approach

Protein tyrosine phosphatase 1B (PTP 1B), a cytosolic PTP involved in down-regulation of receptor tyrosine kinase activity following stimulation of the insulin or leptin receptors. Thus, PTP 1B inhibitors could potentially ameliorate insulin resistance and normalize plasma glucose and insulin levels without inducing hypoglycemia, and could therefore be a major advancement in the treatment of type 2 diabetes. A three-dimensional quantitative structure-activity relationship (3D-QSAR) study has been performed on a novel class of sulphonamides using self-organizing molecular field analysis (SOMFA) to correlate their chemical structures with their observed PTP 1B inhibitory activities. The master grid obtained for the various SOMFA models indicates electrostatic and shape potential contributions that can be mapped back onto structural features relating to the trends in inhibitory activities. On the basis of the spatial arrangement, steric and electrostatic factors should appropriately be taken into account for development of new potent inhibitors of PTP 1B for the management of type 2 diabetes

Direct and indirect drug design approaches for the development of novel tricyclic antipsychotics: potential 5-HT2A antagonist

Schizophrenia is a mental disorder manifested largely by disintegration of thought processes and emotional responsiveness. Given the therapeutic and toxic limitations of clinically available drugs, it is clear that there is still a need for the development of new generation antipsychotic agents with an improved clinical profile. Development of novel hybrid atypical tricyclic antipsychotic pharmacophore was achieved using direct (by measuring docking score of designed molecules on modelled 5- HT 2 A receptor) and indirect (current, clinically available therapeutic agents' data) drug design approaches