Synthesis, Molecular Docking and Biological Evaluation of 2‐Aryloxy‐N‐Phenylacetamide and N′‐(2‐Aryloxyoxyacetyl) Benzohydrazide Derivatives as Potential Antibacterial Agents

Abstract

A new class of 2‐aryloxy‐N‐phenylacetamide and N′‐(2‐aryloxyoxyacetyl) benzohydrazide derivatives with different active moieties were synthesized and screened for their antibacterial activity. Structural characterization of synthesized compounds was performed using HR‐MS, 1H‐NMR, and 13C‐NMR spectral data. Amongst the synthesized compounds, 4‐{2‐[2‐(2‐chloroacetamido)phenoxy]acetamido}‐3‐nitrobenzoic acid (3h) and 2‐chloro‐N‐(2‐{2‐[2‐(2‐chlorobenzoyl)hydrazinyl]‐2‐oxoethoxy}phenyl)acetamide (3o) have shown good antibacterial activity against a selected panel of bacteria. Besides, compounds also exhibited bactericidal activity against P. aeruginosa (3h, 0.69 μg/mL) and S. aureus (3o, 0.62 μg/mL) as evident by MBC and time‐kill kinetics studies. In silico molecular docking and ADMET properties of newly synthesized compounds revealed that compounds could be considered as promising antibacterial agents.

Benzohydrazide and Phenylacetamide Scaffolds: New Putative ParE Inhibitors

“…The MBC of the selected compounds was tested against E. coli and MRSA strains. The MBC of compounds against other organisms was already reported (Yele et al, 2020(Yele et al, , 2021. All the compounds exhibited significant bactericidal activity against E. coli and MRSA strains (Table 2).…”

“…In our earlier work, we reported the synthesis, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), time-kill kinetics of phenylacetamide and benzohydrazides derivatives (1-29) (Supplementary Table 1) (Yele et al, 2020(Yele et al, , 2021. In continuation of our work, we report in vitro MIC and MBC against Escherichia coli (NCIM 2065) (E. coli), methicillin-resistant Staphylococcus aureus (MRSA) (NCIM 5021 and ATCC 43300).…”

“…AST was performed on the compounds (1-29) (Supplementary Table 1) (Yele et al, 2020(Yele et al, , 2021 concerning the standard protocol (CLSI, 2017). The lowest concentration of a compound at which inhibition of bacterial growth was observed is termed MIC.…”

“…MBC can be defined as the minimum concentration of a compound required to kill the bacteria over a fixed period under precise conditions. MBC was determined for the synthesized compounds (1-29) (Supplementary Table 1; Yele et al, 2020Yele et al, , 2021 concerning the standard protocol (CLSI, 2017). Three successive concentrations above the MIC were employed, and 20 µL of the aliquot were sub-cultured onto the prepared nutrient agar plates, followed by incubation at 37 • C for 24 h. Colonies were counted, and colony forming unit (CFU) per milliliter was calculated.…”

“…The MIC of the selected compounds was determined in the concentration range of 0.625-20 µg/mL against E. coli and MRSA strains. The MIC of compounds against other organisms was already reported (Yele et al, 2020(Yele et al, , 2021. The obtained MIC values are compared with standard drug ciprofloxacin, and the results are given in Table 1.…”