2D-QSAR in hydroxamic acid derivatives as peptide deformylase inhibitors and antibacterial agents.

Peptide deformylase catalyzes the removal of N-formyl group from the N-formylmethionine of ribosome synthesized polypeptide in eubacteria. Quantitative structure-activity relationship (QSAR) studies have been carried out in a series of beta-sulfonyl and beta-sulfinyl hydroxamic acid derivatives for their PDF enzyme inhibitory and antibacterial activities against Escherichia coli DC2 and Moraxella catarrhalis RA21 which demonstrate that the PDF inhibitory activity in cell free and whole cell system increases with increase in molar refractivity and hydrophobicity. The comparison of the QSARs between the cell free and whole cell system indicate that the active binding sites in PDF isolated from E. coli and in M. catarrhalis RA21 are similar and the whole cell antibacterial activity is mainly due to the inhibition of PDF. Apart from this the QSARs on some matrixmetelloproteins (COL-1, COL-3, MAT and HME) and natural endopeptidase (NEP) indicate the possibilities of introducing selectivity in these hydroxamic acid derivatives for their PDF inhibitory activity.