Synthesis and quantitative structure activity relationship (QSAR) of arylidene (benzimidazol-1-yl)acetohydrazones as potential antibacterial agents

Abstract

Ethyl (benzimidazol-1-yl)acetate was subjected to hydrazinolysis with hydrazine hydrate to give (benzimidazol-1-yl)acetohydrazide. The latter was reacted with various aromatic aldehydes to give the respective arylidene (1H-benzimidazol-1-yl)acetohydrazones. Solutions of the prepared hydrazones were found to contain two geometric isomers. Similarly (2-methyl-benzimidazol-1-yl)acetohydrazide was reacted with various aldehydes to give the corresponding hydrazones. The antibacterial activity was evaluated in vitro by minimum inhibitory concentration (MIC) against Agrobacterium tumefaciens (A. tumefaciens), Erwinia carotovora (E. carotovora), Corynebacterium fascians (C. fascians) and Pseudomonas solanacearum (P. solanacearum). MIC result demonstrated that salicylaldehyde(1H-benzimidazol-1-yl)acetohydrazone (4) was the most active compound (MIC = 20, 35, 25 and 30 mg/L against A. tumefaciens, C. fascians, E. carotovora and P. solanacearum, respectively). Quantitative structure activity relationship (QSAR) investigation using Hansch analysis was applied to find out the correlation between antibacterial activity and physicochemical properties. Various physicochemical descriptors and experimentally determined MIC values for different microorganisms were used as independent and dependent variables, respectively. pMICs of the compounds exhibited good correlation (r = 0.983, 0.914, 0.960 and 0.958 for A. tumefaciens, C. fascians, E. carotovora and P. solanacearum, respectively) with the prediction made by the model. QSAR study revealed that the hydrophobic parameter (ClogP), the aqueous solubility (LogS), calculated molar refractivity, topological polar surface area and hydrogen bond acceptor were found to have overall significant correlation with antibacterial activity. The statistical results of training set, correlation coefficient (r and r (2)), the ratio between regression and residual variances (f, Fisher's statistic), the standard error of estimates and significant (s) gave reliability to the prediction of molecules with activity using QSAR models. However, QSAR equations derived for the MIC values against the tested bacteria showed negative contribution of molecular mass.

Synthesis, computer‐aided ADMET prediction, and molecular docking of novel 3,5,6‐trichloropyridin‐2‐yl derivatives as potential antimicrobial agents

“…However, the yields of compounds 1 and 8 were 95 and 94%, respectively (Table 1). The chemical structures of the synthesized compounds were confirmed by 1 H-NMR (Figures S1a-S8a), 13 C-NMR (Figures S1b-S8b), and MS (Figures S1c-S8c). In 1 H-NMR spectra, only one hydrogen of pyridine moiety was shown as a single signal at a chemical shift between 8.24 to 8.34 ppm.…”

“…The antibacterial activity of the synthesized compounds 1–8 was carried out in 96‐well microtiter plates using the broth microdilution method [ 12,13 ] compared to amoxicillin as a standard drug. A Gram‐positive bacterium S. aureus ATCC 6538 was obtained from the Microbiology Laboratory, Department of Dairy Science, Faculty of Agriculture, and the Alexandria University, Egypt.…”

“…Melting points were determined by an open capillary method using a Griffin melting point apparatus. The spectra of the synthesized compounds were identified and confirmed by 1 H-NMR and 13 C-NMR spectra using a Bruker NMR (400 MHz, Germany). Deuterated dimethyl sulphoxide (DMSO) was used as a solvent.…”

“…In 13 C-NMR spectra, the C4 of pyridine of all synthesized compounds appeared at δ 137-142 ppm. The carbon atoms of carbonyl groups of the products 1, 2, 3, 7, and 8 were found at δ 180.03, 207.34, 202.53, 165.65, and 163.12 ppm, respectively.…”

In Vitro Antimicrobial and Antioxidant Activities of Monoterpenes against some Food-Borne Pathogens

“…The cultures were maintained on (NA: Peptone 5 g, Beef extract 3 g, NaCl 8 g) nutrient agar medium at 37ºC. The antibacterial activities of the monoterpenes were evaluated out in 96-well microtiter plates according (Aruna Kumari et al 2017;El-Kilany et al 2015). It has been diluted with (NB) sterile Nutrient broth medium to a concentration of 5×105 CFU/mL calculated as a number of colonies× dilution factor/volume of culture plate using hemocytometer.…”