Synthesis and Antibacterial Activity of Novel Hydroxy Semicarbazone Derivatives

Abstract

A series of hydroxyl semicarbazone derivatives of substituted diaryl ketones and acetophenones were synthesized and their structures were confirmed by analytical and spectroscopic methods including elemental analysis, infrared and nuclear magnetic resonance spectroscopy. The derivatives were prepared by a condensation reaction between N-hydroxy semicarbazide and substituted diaryl ketones or acetophenones leading to the desired hydroxysemicarbazones with excellent purity. The synthesized hydrazones were then evaluated for their inhibitory activity against bacterial strains including S. aureus, E. Coli, P. aeruginosa, K. pneumonia and M. luteus. Among the tested derivatives, compounds 2, 6 and 7 exhibited the highest bioactivity. Analysis of the activity data suggests that hydrophilicity is an important factor for the bioactivity of compounds 2 and 6 and also their selectivity over the gram-negative bacteria.

Keywords: Antibacterial; Broth microdilution assay; Hydrophilicity; Ketones; N-hydroxy semicarbazone.

Figure 1

General structure of active (thio) semicarbazones. X = O, S; R = various aromatic and aliphatic substituents

Figure 2

Antimycobacterial N-hydroxy semicarbazone derivatives reported by Sriram et al. (8).

Figure 3

Design of the novel N-hydroxy semicarbazone derivatives based on the structural elements of active N-hydroxy thiosemicarbazones (left) and semicarbazones (right

Scheme 1

Synthesis of N-hydroxy semicarbazones 1-6

Figure 4

Structures of E (right) and Z (left) isomers of compound 3