Due to the uneven distribution of glycosidase enzyme expression across bacteria and fungi, glycoside derivatives of antimicrobial compounds provide prospective and promising antimicrobial materials. Therefore, herein, we report the synthesis and characterization of six novel methyl 4,6-O-benzylidene-α-d-glucopyranoside (MBG) derivatives (2–7). The structures were ascertained using spectroscopic techniques and elemental analyses. Antimicrobial tests (zone of inhibition, MIC and MBC) were carried out to determine their ability to inhibit the growth of different Gram-positive, Gram-negative bacteria and fungi. The highest antibacterial activity was recorded with compounds 4, 5, 6 and 7. The compounds with the most significant antifungal efficacy were 4, 5, 6 and 7. Based on the prediction of activity spectra for substances (PASS), compounds 4 and 7 have promising antimicrobial capacity. Molecular docking studies focused on fungal and bacterial proteins where derivatives 3 and 6 exhibited strong binding affinities. The molecular dynamics study revealed that the complexes formed by these derivatives with the proteins L,D-transpeptidase Ykud and endoglucanase from Aspergillus niger remained stable, both over time and in physiological conditions. Structure–activity relationships, including in vitro and in silico results, revealed that the acyl chains [lauroyl-(CH3(CH2)10CO-), cinnamoyl-(C6H5CH=CHCO-)], in combination with sugar, were found to have the most potential against human and fungal pathogens. Synthetic, antimicrobial and pharmacokinetic studies revealed that MBG derivatives have good potential for antimicrobial activity, developing a therapeutic target for bacteria and fungi. Furthermore, the Petra/Osiris/Molinspiration (POM) study clearly indicated the presence of an important (O1δ−----O2δ−) antifungal pharmacophore site. This site can also be explored as a potential antiviral moiety.
The present study is focused on the synthesis of methyl-4,6-O-benzylidene-α-D-glucopyranoside (MBG) derivatives and on the characterization of their biological properties. Their structures were revealed by spectroscopic characterization and antimicrobial activities were evaluated in vitro against human and plant microorganisms along with the prediction of substance activity spectra. Minimum inhibition concentration (0.675±0.01 to 1.35±0.01 mg/ml) and minimum bactericidal concentration (1.35±0.01 to 5.40±0.04 mg/ml) tests were conducted for two compounds (4 and 7) based on their activity. X-ray powder diffraction was employed for quantitatively identifying crystalline compounds. Molecular docking studies focused on fungal proteins and bacterial proteins where derivatives 3 and 6 exhibited very strong binding and inhibitory affinities. Also, the molecular dynamics study carried out revealed that the complexes formed by these derivatives with the proteins L,D-transpeptidase Ykud and endoglucanase from Aspergillus niger can remain stable both over time and in physiological conditions. Structure-activity relationships study including in vitro and silico results revealed that the acyl chains [lauroyl (C12), cinnamoyl (C6H5CH=CHCO-)] in combination with sugar were found the most potential activates against human and fungal pathogens. Our synthetic, antimicrobial, and pharmacokinetic studies revealed that MBG derivatives have promising antimicrobial activity, which could develop a therapeutic target for bacteria and fungi.
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