Novel Chloro-Substituted Salicylanilide Derivatives and Their β-Cyclodextrin Complexes: Synthesis, Characterization, and Antibacterial Activity

Abstract

The goal of this research was to design novel chloro-substituted salicylanilide derivatives and their β-cyclodextrin complexes in order to obtain efficient antibacterial compounds and to demonstrate the beneficial role of complexation on the efficiency of these compounds. Thus, salicylanilide derivatives, esters, and hydrazides were obtained by microwave-assisted synthesis and their structure proven based on FTIR and NMR spectra. In order to improve water solubility, chemical and physical stability, and drug distribution through biological membranes, the inclusion complexes of the ethyl esters in β-cyclodextrin were also obtained using kneading. Inclusion-complex characterization was accomplished by modern analytical methods, X-ray diffraction, SEM, TGA, FTIR, and UV-vis spectroscopy. The newly synthesized compounds were tested against some Gram-positive and Gram-negative bacteria. Antimicrobial tests revealed good activity on Gram-positive bacteria and no inhibition against Gram-negative strains. The MIC and MBC values for compounds derived from N-(2-chlorophenyl)-2-hydroxybenzamide were 0.125–1.0 mg/mL. N-(4-chlorophenyl)-2-hydroxybenzamide derivatives were found to be less active. The inclusion complexes generally behaved similarly to the guest compounds, and antibacterial activity was not been altered by complexation.

Preparation and Characterization of a Novel Salicin–Cyclodextrin Complex

“…). Thus, due to the complexation phenomenon, the encapsulated product exhibits a broadening of the diffraction peaks meaning a lower degree of crystallinity, which confirm the inclusion and the amorphous nature of the complex [53,54].…”

“…The XRD spectra of inclusion complex (IC) reveals a drastic reduction in intensity of some spectral lines corresponding to salicin (8.4°, 16.8°, 25.3°, 26.4°, 30.0°, 31.6°, 43.1°) and β-cyclodextrin (10.7°, 12.5°, 17.2°, 19.7°, 23.0°, 24.4°, 27.1°). Thus, due to the complexation phenomenon, the encapsulated product exhibits a broadening of the diffraction peaks meaning a lower degree of crystallinity, which confirm the inclusion and the amorphous nature of the complex [ 53 , 54 ].…”

“…Similarly, the band assignable to glycosidic ν[C–O–C] shifts from 1238.24 to 1240.17 cm −1 . The increase in frequency can be attributed to the increase in electron cloud density simultaneously with the inclusion of the benzene nucleus inside the β-cyclodextrin cavity [ 54 , 55 ]. Also, the decrease in intensity of the specific bands of salicin in the IC can be ascertained.…”

“…Moreover, the physical mixture (328.2 °C) revealed also a greater stability than the neat components, suggesting the benefits of the β-cyclodextrin presence on the stability of salicin. All these phenomena show that the formation of the inclusion complex altered the thermal degradation properties of the two components as such [ 54 ].…”

Halogenated Antimicrobial Agents to Combat Drug-Resistant Pathogens

“…Although the phenolic group on the scaffold seems to confer antimicrobial activity, it is sometimes responsible for irritation and uncoupling activity. Hence, modification is required to temporarily block these activities and improve membrane penetration, bioavailability, and bioactivity (Ienașcu et al, 2022). Halogenated salicylanilide derivatives were reported as anthelmintic agents, disinfectants, and antimicrobial agents against resistant pathogens.…”