Synthesis and antimicrobial evaluation of 3-hydrazino-naphthoquinones as analogs of lapachol

Several 1,4-naphthoquinone derivatives having a hydrazino side chain were synthesized from 3-diazo-naphthalene-1,2,4-trione and tested as potential antimicrobial agents. These naphthoquinone derivatives 2-[N'-(1-acetyl-2-oxo-propylidene)-hydrazino]-3-hydroxy-[ 1,4] naphthoquinone, ethyl 2-[(3-hydroxy-1,4-dioxo-1,4-dihydro-naphthalen-2-yl)-hydrazono] 3-oxo-butyrate, t-butyl 2-[(3-hydroxy-1,4-dioxo-1,4-dihydro-naphthalen-2-yl)-hydrazono]-3-oxobutyrate, 3-hydroxy-2-[(di-O-isopropylidene-malonate)-hydrazino]-1,4-naphthoquinone, and diethyl 2-[(3-hydroxy-1,4-dioxo-1,4-dihydro-naphthalen-2-yl)-hydrazono]-malonate showed greater antibacterial activity at the level of the preliminary susceptibility testing in disk than lapachol (1), a well known 1,4-naphthoquinone which has several biological activities. Studies on the minimal inhibitory concentration (MIC) for Staphylococcus aureus showed that diethyl 2-[( 3-hydroxy-1,4-dioxo-1,4-dihydro-naphthalen-2-yl)-hydrazono]- malonate has an activity twofold greater than 1. On the other hand, optical density measurement for S. aureus indicated that this compound has similar activity compared with vancomycin at 2xMIC.