Pharmacophore based 3D-QSAR study of matrix metalloproteinase (MMPs) inhibitors

Author(s): Divya Rastogi, Sachi Mittal, P.P.Singh

Matrix metalloproteinase (MMPs also known as metzincins generally expressed in very low amounts and their transcription is tightly regulated either positively or negatively by cytokines and growth factors or tumor necrosis factor. MMPs dealing with various aspects of their physiologic and pathologic roles in biologic processes. Therefore, inhibitors ofMMPs have several interests. In order to understand the possible interactions and necessary structural features we have derived common pharmacophore hypotheses (CPHs) among a series of hydroxamate derivatives using PHASE module of Schrödinger suit. The study implies that a hydrophobic centre along with four different hydrogen bond acceptor site with in a set of conditions was common to all the derivativs. This CPH has significantly contributed (q2=0.92, r2=0.94, F=55.2) to inhibitory activity. Overall, the Pharmacophore models have given an insight to the importance of hydrophobic and hydrogen bond acceptor groups which is helpful for further modification and designing of such inhibitors.

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