Synthesis and Biological Evaluation of Benzo[b]thiophene Acylhydrazones as Antimicrobial Agents against Multidrug-Resistant Staphylococcus aureus

Abstract

The benzo[b]thiophene nucleus and the acylhydrazone functional group were combined to prepare three new series of compounds for screening against Staphylococcus aureus. The reaction of substituted benzo[b]thiophene-2-carboxylic hydrazide and various aromatic or heteroaromatic aldehydes led to a collection of 26 final products with extensive structural diversification on the aromatic ring and on position 6 of the benzo[b]thiophene nucleus. The screening lead to the identification of eight hits, including (E)-6-chloro-N’-(pyridin-2-ylmethylene)benzo[b]thiophene-2-carbohydrazide (II.b), a non-cytotoxic derivative showing a minimal inhibitory concentration of 4 µg/mL on three S. aureus strains, among which were a reference classical strain and two clinically isolated strains resistant to methicillin and daptomycin, respectively.

Importance of the 2,6-Difluorobenzamide Motif for FtsZ Allosteric Inhibition: Insights from Conformational Analysis, Molecular Docking and Structural Modifications

“…The antimicrobial activity was assessed by determining the corresponding MIC values against three S. aureus strains: a reference strain (ATCC29213), a methicillin-resistant strain (SF8300) [34] and a clinically isolated daptomycin-resistant strain (ST20171643) [35] (Table 1). 3-HBA and DFHBA, used as references, exert MIC values of 256 µg/mL and 8 µg/mL consistent with the literature [14][15][16].…”

Structural Variations in the Central Heterocyclic Scaffold of Tripartite 2,6-Difluorobenzamides: Influence on Their Antibacterial Activity against MDR Staphylococcus aureus

“…The series I , II , III , and IV were tested for their antimicrobial activity on three strains of S. aureus , including a reference (ATCC 29213) and two clinically isolated strains respectively resistant to methicillin (SF8300) [ 16 ] and daptomycin (ST20171643) [ 17 ], with PC190723 as control. The purpose of this experiment was to establish the minimum inhibitory concentration (MIC), which is the minimum concentration of compound needed to prevent the growth of a standardized bacterial inoculum, for the triazole and oxadiazole series.…”

Facile synthesis of substituted 2-aroylbenzo[b]thiophen-3-ols to form novel triazole hybrids using click chemistry

“…6,7 Benzo[b]thiophene is a versatile sulfur-containing heterocyclic scaffold, which frequently appears in pharmaceutically interesting compounds with a diverse range of biological activities. [8][9][10][11][12] For instance, various drugs including raloxifene (1), arzoxifene (2), rintodestrant (3), and LSZ102 (4) feature the benzo[b]thiophene core and are currently clinically utilized for the treatment of estrogen-receptor-positive breast cancer (Fig. 1).…”