The QSAR study for antibacterial activity of structurally diverse nitroaromatics

  • Jonas Šarlauskas
  • Evelina Polmickaitė-Smirnova
  • Narimantas Čėnas
  • Kastis Krikštopaitis
  • Žilvinas Anusevičius
Keywords: nitroaromatic compounds, antibacterial activity, QSAR, quantum mechanical computation, DFT


The antibacterial activity of a series of structurally diverse nitroaromatic compounds (NACs) (nitrobenzene and nitroheterocyclic derivatives) was estimated in terms of the minimum inhibitory concentrations (MICs) against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria strains in vitro. The resultant log of 1/MICs (pMICs) was subjected to a quantitative structure–activity relationship analysis (QSAR) using a set of molecular descriptors of the compounds assessed by means of quantum mechanical computation and other methods. The estimated pMIC values of NACs tentatively increased with an increase in their electrophilic potency (in terms of LUMO energy) along with the LUMO–HOMO energy gap (or chemical hardness) towards both bacteria strains. No reliable contribution of lipophilicity (octanol/water log P) of nitroaromatics was found to both bacteria strains. The activity of NACs towards S. aureus increased with an increase in their molecular weight and van der Waals volume, and it also tended to increase with an increase in their polar surface area (PSA) and in the number of hydrogen bond-acceptors (HBAs), whereas using these descriptors against E. coli strain, no satisfactory correlations were obtained. The activity of NACs towards both bacteria strains showed a parabolic type dependence upon the highest positive values of molecular electrostatic potentials (VS, max) that might partially be associated with the non-specific interaction of nitroaromatics with the surfaces of the negatively charged envelopes of bacteria at the initial stage of NACs’ action.
Organic Chemistry