The QSAR study for antibacterial activity of structurally diverse nitroaromatics

Abstract

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.

Synthesis of some pyrrolidine‐2,5‐dione derivatives with biological activity against Gram‐negative bacteria

“…This premise is supported by some theoretical studies which suggest that biological activity of several compounds depends on chemical fragments such as tropilidine ring, [70] quinolone system, [71] indole fragment. [72] Table 3…”

Quantitative Structure-Activity Relationship (QSAR) Studies on the Toxic Effects of Nitroaromatic Compounds (NACs): A Systematic Review

“…According to previous studies, the octanol-water partition coefficient (LogP/KOW/logKOW) is an indispensable factor in chemical toxicity [1,4,24,31,41,44,[46][47][48]. In some cases, though, the determinant factors of toxicity need to be replenished to account for specific phenomena like ionization [49].…”

Convenient Preparation, Thermal Properties and X-ray Structure Determination of 2,3-Dihydro-5,6,7,8-tetranitro-1,4-benzodioxine (TNBD): A Promising High-Energy-Density Material

“…Later, in the same laboratory, the nitro and amino derivatives of 1,4-benzodioxane were used as a core structural fragment for the synthesis of novel annulated O,N-heterocyclic derivatives [43][44][45][46][47].…”