Anti-staphylococcal effect of plant-derived stilbenes

Ing. Tereza Žáková

Doctoral thesis

Abstract:

Staphylococcus aureus is a deadly pathogen that was initially limited to hospital and healthcare facilities but has gradually become a growing problem in healthy children and adults. Stilbenes are polyphenol compounds of plant origin known to possess a variety of pharmacological properties such as antibacterial, antiviral, and antifungal effects. This study reports the in vitro growth-inhibitory potential of eight naturally occurring stilbenes against six standard strains and two clinical isolates of S. aureus, using a broth microdilution method, and expressing the results as minimum inhibitory concentrations (MICs). Pterostilbene (MICs 32 - 128 µg/ml), piceatannol (MICs 64 - 256 µg/ml) and pinostilbene (MIC 128 µg/ml) are among active compounds that possessed the strongest activity against all microorganisms tested, followed by 3′-hydroxypterostilbene, isorhapontigenin, oxyresveratrol and rhapontigenin with MICs 128 - 256 µg/ml. Resveratrol (MIC 256 µg/ml) exhibited only weak inhibitory effect against two standard S. aureus strains ATCC 25923 and ATCC 33592. Furthermore, structure–activity relationships were studied. Hydroxyl groups at ortho-position (B-3´, -4´) played crucial role for the inhibitory effect of hydroxystilbene piceatannol. Compounds with methoxy groups at the ring A (3′-hydroxypterostilbene, pinostilbene and pterostilbene) produced stronger effect against S. aureus than their analogues (isorhapontigenin and rhapontigenin) with methoxy groups at the ring B. Resveratrol has been described to possess several biological activities such as antioxidant, antimicrobial and anti-inflammatory. However, its efficacy is still limited owing to its low aqueous solubility. Cyclodextrins and their derivatives have the ability to encapsulate the bioactive compounds into its cavity and protect these from the environmental conditions, improve the solubility and bioavailability. Therefore, another goal of this study was the evaluation of resveratrol complex with β-cyclodextrine against standard strains of S. aureus. In our tests resveratrol complex showed moderate activity with the MIC value of 256 µg/ml for one standard S. aureus strain ATCC 33591. These findings provide arguments for further investigation of stilbenes as prospective structures for development of novel anti-staphylococcal agents. Moreover, stilbene encapsulation with β-cyclodextrine may increase their anti-staphylococcal potential.

Keywords

natural antibacterial agents, antimicrobial activity, minimum inhibitory concentration, stilbenes, Staphylococcus aureus, structure–activity relationships, β-cyclodextrine

Language used: English

Date on which the thesis was submitted / produced: 27. 5. 2019

Thesis defence

• Supervisor: prof. Ing. Ladislav Kokoška, Ph.D.
• Reader: Jiří Killer, externi, Jaroslav Havlík, externi, Zsófia Kutil, Bc., externi

Czech University of Life Sciences Prague

Faculty of Tropical AgriSciences

Doctoral programme / field:
Agricultural Specialization / Tropical Agrobiology and Bioresource Management