Synthesis and Bioactivity Evaluation of Novel 2-Salicyloylbenzofurans as Antibacterial Agents.

Phuong-Thuy Phan,Thao Vu,Hong-Nhung Nguyen,Bao-Khanh Le,Thu-Trang Nguyen,Dong Tran,Tuan-Anh Pham

doi:10.3390/molecules22050687

Abstract

In order to discover new antibacterial agents, series of 2-salicyloylbenzofuran derivatives were designed, synthesized and evaluated for their antibacterial activities against three Gram-(+) strains (methicillin-sensitive Staphylococcus aureus (MSSA) ATCC 29213, methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, and Streptococcus faecalis (S. faecalis) ATCC 29212) and one Gram-(−) strain (Escherichia coli (E. coli) ATCC 25922). The 2-salicyloylbenzofuran heterocycles were generated by Rap–Stoermer condensation of salicylaldehydes with phenacyl bromides and then converted to diverse O-ether derivatives by Williamson synthesis. The targeted products were screened for in vitro qualitative (zone of inhibition) and quantitative (MIC) antibacterial activities by agar well diffusion assay and agar dilution method. Amongst the compounds, those bearing carboxylic acid functional group were found to exhibit reasonable activity against Gram-(+) bacterial strains including S. faecalis, MSSA and MRSA with the most potent antibacterial agent 8h (MICs = 0.06–0.12 mM). Besides, the 2-salicyloylbenzofurans partly displayed inhibitory activity against MRSA with the best MICs = 0.14 mM (8f) and 0.12 mM (8h). Finally, the antibacterial results preliminarily suggested that the substituent bearing carboxylic acid group at salicyloyl-C2 and the bromine atoms on the benzofuran moiety seem to be the functionality necessary for antibacterial activities.

Highlights

Drug resistant infections are complex problems that have been threatening the health care with related morbidity and mortality being on the rise worldwide
We found 0that the naturally diaryl(heteroaryl)ketone scaffold such as pestalone [5], pyrrolomycins including 3,4,5,3,50 -pentabromo-2-(20 -hydroxybenzoyl)pyrrole [10] and fluorinated marinopyrrole A–F [6,7], pyrrolomycin C [8], pyrrolomycin J [9], and synthetic compounds related to pyrrolomycines
Bromination of starting material 2-methoxyacetophenone using NBS as bromine source in the presence of p-toluenesulfonic acid (PTSA) gave 21 using NBS as bromine source in the presence of p-toluenesulfonic acid (PTSA) gave methoxyphenacyl bromide 2 [17] that was reacted with 3,5-dibromosalicyladehyde via Rap–Stoermer

Summary

Introduction

Drug resistant infections are complex problems that have been threatening the health care with related morbidity and mortality being on the rise worldwide. 2 of 13 new drugs from existing classes of antibiotics that can effectively against the multidrug-resistant bacterial discovery strains [1,2,4]. Development of new classes of antibacterial agents as well as exploring possible new drugs from existing classes of antibiotics that can effectively against the multidrug-resistant bacterial. We found 0that the naturally diaryl(heteroaryl)ketone scaffold such as pestalone [5], pyrrolomycins including 3,4,5,3 ,50 -pentabromo-2-(20 -hydroxybenzoyl)pyrrole [10] and fluorinated marinopyrrole A–F [6,7], pyrrolomycin C [8], pyrrolomycin J [9], and synthetic compounds related to pyrrolomycines [11], displayed strong inhibitory activities against bacterial.

Methods

Results

Conclusion