Synthesis and Antibacterial Activity of New Azole, Diazole and Triazole Derivatives Based on p-Aminobenzoic Acid.

Birutė Sapijanskaitė-Banevič,Rita Vaickelionienė,Birutė Grybaitė,Vykintas Palskys,Jūratė Šiugždaitė,Povilas Kavaliauskas,Vytautas Mickevičius

doi:10.3390/molecules26092597

Abstract

The p-aminobenzoic acid was applied for the synthesis of substituted 1-phenyl-5-oxopyrrolidine derivatives containing benzimidazole, azole, oxadiazole, triazole, dihydrazone, and dithiosemicarbazide moieties in the structure. All the obtained compounds were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus, Bacillus cereus, Listeria monocytogenes, Salmonella enteritidis, Escherichia coli, and Pseudomonas aeruginosa by using MIC and MBC assays. This study showed a good bactericidal activity of γ-amino acid and benzimidazoles derivatives. The antimicrobial activity of the most promising compounds was higher than ampicillin. Furthermore, two benzimidazoles demonstrated good antimicrobial activity against L. monocytogenes (MIC 15.62 µg/mL) that was four times more potent than ampicillin (MIC 65 µg/mL). Further studies are needed to better understand the mechanism of the antimicrobial activity as well as to generate antimicrobial compounds based on the 1-phenyl-5-oxopyrrolidine scaffold.

Highlights

Growing antimicrobial resistance (AMR) has become a major source of morbidity and mortality worldwide [1]
Considering the wide structural and biological diversity of p-aminobenzoic acid and its derivatives, we present the synthesis and antibacterial evaluation of a series of 1-(4-carboxyphenyl)-5-oxopyrrolidine-3-carboxylic acid derivatives using p-aminobenzoic acid as the starting compound (Scheme 1)
The interaction of dihydrazide 10 with phenyl isothiocyanate in refluxing methanol led to the formation of thiosemicarbazide 12, which under the action of 4% sodium hydroxide at reflux for 6 h and subsequent acidification of the mixture with dilute hydrochloric acid (1:1) to pH 2 afforded heterocyclic compound 13 with two 4-phenyl-5-thioxo-1,2,4triazole moieties in the structure

Summary

Introduction

Growing antimicrobial resistance (AMR) has become a major source of morbidity and mortality worldwide [1]. The genetic determinants encoding AMR phenotypes can be further disseminated via horizontal gene transfer and accumulate in various bacterial species [10,11]. These processes created a vicious cycle that gave rise to multidrug-resistant (MDR) pathogens harboring multiple resistance mechanisms, resulting in bacterial resistance to two and more antimicrobial drugs [12]. To overcome this problem, it is important to develop novel compounds targeting MDR pathogens

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