Design, Synthesis and <i>in Vitro</i> Antibacterial Activity of 2-thiomethyl-benzimidazole Derivatives

Abstract

A series of novel substituted benzimidazole (7a -n) derivatives were synthesized and characterized by 1 H, 13 C Nuclear Magnetic Resonance (NMR) spectra and High Resolution Mass Spectrometry (HRMS). The substitution was done in position -1 and -2 by appropriate groups. These compounds are obtained by N-alkylation reaction with thiomethyl-1H-benzimidazole intermediates (5a -g). Design of intermediates (5a -g) was made by condensation reaction between 2-methylbenzimidazole thiourunium salt (3) and functionalized halides (4) in the presence of sodium hydroxide (NaOH). Among the twenty-one compounds synthesized, ten were evaluated for their antimicrobial activity on three bacterial strains namely: Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853. Only E. coli ATTC 25922 was susceptible to the synthesized derivatives 5g, 7f and 7h with a significant antibacterial activity (CMI is between 250 and 500 μg/mL).

Exploration of Remarkably Potential Multitarget-Directed N-Alkylated-2-(substituted phenyl)-1H-benzimidazole Derivatives as Antiproliferative, Antifungal, and Antibacterial Agents

“…Because of the poor qualitative activity by the disk diffusion test of all 1 H -benzimidazole derivatives ( 1 – 3 ), none were further tested for MIC. Moreover, strain P. aeruginosa was not susceptible to a series of N-alkylated 1 H -benzimidazole ( 1a − g , 2a − g , and 3a − g ), similar to the results of Evrard et al (2021) . Compounds 1a – b , 2a – b , 2g , and 3a showed weak-to-moderate activity against Gram-negative bacteria ( E. coli ), with MIC values ranging from 64 to 1024 μg mL –1 .…”

“…Moreover, strain P. aeruginosa was not susceptible to a series of N-alkylated 1 H -benzimidazole ( 1a − g , 2a − g , and 3a − g ), similar to the results of Evrard et al (2021). 50 Compounds 1a – b , 2a – b , 2g , and 3a showed weak-to-moderate activity against Gram-negative bacteria ( E. coli ), with MIC values ranging from 64 to 1024 μg mL –1 . The findings revealed that these 1-alkyl-2-(substituted phenyl) benzimidazole derivatives may be ineffective at inhibiting the growth of Gram-negative bacteria.…”

Benzimidazoles and Imidazo[1,2-a]pyridines : Biological Activities, Method of Synthesis and Perspectives on Combination of Deuce Pharmacophore

“…22 and Pseudomonas aeruginosa ATCC 27853. 23 Twelve (12) N-alkyl 2-benzylthiomethyl-1H-benzimidazole derivatives were evaluated and their antibacterial profile was determined with minimal inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs). The results showed that compounds 8a, 8b, 8c, 8d, 8e, 8f, 8h, 8k, and 8l were potent against Escherichia coli and Staphylococcus aureus, with significant MICs values from 140 to 290 µg/mL.…”

A Review on Benzimidazole Heterocyclic Compounds: Synthesis and Their Medicinal Activity Applications

“…Many of the prepared derivatives have efficacy comparable or superior to the standard drugs used for the same purpose. [138][139][140][141][142][143][144][145][146][147][148][149][150][151][152][153]…”