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Asian Journal of Biochemistry

Year: 2006 | Volume: 1 | Issue: 1 | Page No.: 47-56
Research Article

Quantitative Structure-activity Relationship Studies on Benzodiazepine Hydroxamic Acid Inhibitors of Matrix Metalloproteinases and Tumor Necrosis Factor-α Converting Enzyme

S.P. Gupta
Department of Chemistry, Birla Institute of Technology and Science, Pilani-333031, India
S. Kumaran
Department of Pharmacy, Birla Institute of Technology and Science, Pilani-333031, India
A Quantitative Structure-activity Relationship (QSAR) study has been made on the inhibitions of some Matrix Metalloproteinases (MMPs) and Tumor Necrosis Factor-α Converting Enzyme (TACE) by benzodiazepine hydroxamic acid inhibitors. It has been found that there exits an inverse parabolic relationship between the hydrophobicity (logP) and inhibition activities of compounds for certain series of inhibitors against MMP-1 and MMP-13, suggesting that inhibition mechanism of these enzymes could be allosteric. The appearance of E-state index of nitrogen atom (SN) attached to sulfonyl group in the equations derived for MMP-9, MMP-13 and TACE reveals that there can be some electronic interaction also between the inhibitors and these enzymes.
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