Bactericidal Effect of Pterostilbene Alone and in Combination with Gentamicin against Human Pathogenic Bacteria

Abstract

The antibacterial activity of pterostilbene in combination with gentamicin against six strains of Gram-positive and Gram-negative bacteria were investigated. The minimum inhibitory concentration and minimum bactericidal concentration of pterostilbene were determined using microdilution technique whereas the synergistic antibacterial activities of pterostilbene in combination with gentamicin were assessed using checkerboard assay and time-kill kinetic study. Results of the present study showed that the combination effects of pterostilbene with gentamicin were synergistic (FIC index < 0.5) against three susceptible bacteria strains: Staphylococcus aureus ATCC 25923, Escherichia coli O157 and Pseudomonas aeruginosa 15442. However, the time-kill study showed that the interaction was indifference which did not significantly differ from the gentamicin treatment. Furthermore, time-kill study showed that the growth of the tested bacteria was completely attenuated with 2 to 8 h treatment with 0.5 × MIC of pterostilbene and gentamicin. The identified combinations could be of effective therapeutic value against bacterial infections. These findings have potential implications in delaying the development of bacterial resistance as the antibacterial effect was achieved with the lower concentrations of antibacterial agents.

In Silico-Mediated Virtual Screening and Molecular Docking Platforms for Discovery of Non β-Lactam Inhibitors of Y-49 β-Lactamase from Mycobacterium Tuberculosis

“…Our motivation to investigate and determine whether there was a structure-activity relationship (SAR) between different stilbenes/resveratrol compounds and their anti-β-lactamase activity was also supported by all previous work reported on these pharmacological agents as inhibitors of some MTB strains growth. [16][17][18][19]39,40 In 1944 Faulkner discovered the bactericidal properties of some stilbenes and diphenyl derivatives. 19 The common structural feature for all tested compounds displaying bactericidal properties was the presence of one or more phenolic-type hydroxyl groups attached to the ring, and ethyl groups between the rings.…”

“…19 The common structural feature for all tested compounds displaying bactericidal properties was the presence of one or more phenolic-type hydroxyl groups attached to the ring, and ethyl groups between the rings. [16][17][18][19] Stilbenes are small molecules with molecular weights in the range of 200 to 300g/mol. They are naturally-occurring plant secondary metabolites and are derived from the phenylpropanoid pathway.…”

“…Stilbenes are structurally similar to estrogen and are produced in many unrelated plant species. [16][17][18] When a plant is subjected to abiotic stress, such as drought, temperature, heavy metals, and salinity, the phenylpropanoid pathway is activated, and stilbenes are produced and secreted. Stilbenes are the plant's protective molecules; they are able to defend the plant from bacterial attack, as well as ultraviolet exposure.…”

“…Stilbenes are the plant's protective molecules; they are able to defend the plant from bacterial attack, as well as ultraviolet exposure. [16][17][18] The most widely studied stilbene is resveratrol which has been shown to slow the progress of cancer. Moreover, it has been known for more than sixty years that resveratrol inhibits bacterial and fungal growth in vitro.…”

“…We first focused on discovery of novel 3D-pharmacophores and fragments from the family of diphenyl, aromatic ketone, hydroxy-phenyl derivatives and stilbene, all previously described by others to exhibit antibacterial activity. [16][17][18][19] The in vitro screening platform, using kinetics of β-lactamase inhibition with nitrocefin substrate, enabled the discovery of potential inhibitors of Y-49 β-lactamase exhibiting inhibitory constants, Ki, in the lowmM range. The finding of these novel pharmacophore features exhibiting anti-β-lactamase inhibition offered additional strength to the structure-based drug design (SBDD) approach by selectively defining the chemical space of the ligand libraries during in silico screening using the on-line server Pharmit (pharmit.csb.pitt.edu) 20 Specifically, we searched different databases of chemical librariesand commercial compounds such as ChEMBL/MolPort/ZINC 21 where the pharmacophore features of the ligands could be chosen to resemble the chemical space of selected stilbenes and other small organic compounds discovered to inhibit the Y-49 β-lactamase using the in vitro, enzymatic screening assay.…”