Adenine and benzimidazole-based mimics of REP-3123 as antibacterial agents against Clostridium difficile and Bacillus anthracis: Design, synthesis and biological evaluation

Abstract

As part of our ongoing research efforts to develop new antibacterial agents acting on novel molecular targets, a series of twenty-two adenine and benzimidazole-based mimics of the lead compound REP-3123 was designed to target methionyl-tRNA synthetase of Clostridium difficile and Bacillus anthracis based on a homology model. Structures of the target compounds were elucidated by means of 1 H and 13 C NMR spectral data and their purity was confirmed by HRMS or microanalyses. The target compounds were tested for their in vitro antibacterial activity against those two challenging organisms by the microdilution method in brain heart infusion broth. Unfortunately, six of the target compounds were not biologically tested due to inadequate solubility in DMSO under the assay conditions. Only the fluoro-substituted adenine-based sulfamide (18) showed activity against C. difficile with an MIC of 85.33 lg/mL. The adenine-based thiourea (32) and diamine (36) were the most promising antibacterial agents against B. anthracis with an MIC of 92.16 lg/mL. The rest of the tested compounds either showed inferior activity (MIC = 102.4 lg/mL) or were totally inactive. Although the compounds were not very active, the biological data are employed as a basis for our currently underway investigation for structure optimization. Ó 2016 Production and hosting by Elsevier B.V. on behalf of Faculty of Pharmacy, Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).

Understanding the Electrochemical Properties of Naphthalene Diimide: Implication for Stable and High-Rate Lithium-Ion Battery Electrodes

“…Therefore, we proposed a possible reaction process between NDI and EC molecules (decarboxylative N-alkylation) that generates the C–OH band. Similar reactions have been found in the hydroxyethylation of imides, oxamides, − and adenines. − Similarly, the possible reaction product, dihydroxylethyl­naphthalene diimide (DHNDI), is shown in Figure c. To confirm the product structure, the 1 H NMR spectrum of the mixture of NDI and EC was obtained (Figure S4), which supports the existence of DHNDI.…”

Design, computational studies, synthesis and in vitro antimicrobial evaluation of benzimidazole based thio-oxadiazole and thio-thiadiazole analogues

“…Methyl 3-(1H-benzo[d]imidazol-1-yl)propanoate (2) was synthesised by a nucleophilic substitution reaction between benzimidazole (1) and methyl 3-bromopropionate in the presence of K 2 CO 3 and 18-crown-6, which is used to enhance the ionisation of K 2 CO 3 in DMF [35][36][37]…”