Design, Synthesis, and Anti-Bacterial Evaluation of Triazolyl-Pterostilbene Derivatives

Abstract

Staphylococcus aureus resistance to current antibiotics has become the greatest global challenge facing public health. The development of new antimicrobial agents is urgent and important and is needed to provide additional therapeutic options. In our previous study, we found out that pterostilbene exhibited potent antibacterial activity, especially against methicillin-resistant Staphylococcus aureus (MRSA). According to previous studies, 1,2,3-triazole, with the characteristic of increasing the interaction with the target readily and enhancing water solubility, were widely used in the approved anti-bacterial drugs. Therefore, these results attract our interest to use the structure of pterostilbene as a scaffold for the hybrid 1,2,3-triazole moiety to develop a novel anti-MRSA infection agent. In this study, we demonstrated the design and synthesis of a series of triazolylpterostilbene derivatives. Among these compounds, compound 4d exhibited the most potent anti-MRSA activity with a minimum inhibitory concentration (MIC) value of 1.2–2.4 μg/mL and a minimum bactericidal concentration (MBC) value of 19.5–39 μg/mL. The structure–activity relationship and antibacterial mechanism were investigated in this study. Molecular docking studies were carried out to verify and rationalize the biological results. In this study, the results confirmed that our design could successfully increase the inhibitory activity and specificity against MRSA. Compound 4d could be used as a candidate for anti-bacterial agents and in depth vivo studies should be further investigated.

Application of triazoles in the structural modification of natural products

“…The accumulated data indicated that presence of the strong electron donating group (OMe) at ortho and para positions of phenyl ring of chalcone could enhance the antibacterial activity of the other products. In contrast, triazolyl-pterostilbene derivatives exhibited potent antibacterial activity, particularly against methicillin-resistant Staphylococcus aureus (MRSA) 126 . Among these compounds, compound 55 ( Figure 11 ) exhibited the most potent anti-MRSA activity with a minimum inhibitory concentration (MIC) value of 1.2–2.4.…”

Tellimagrandin II, A Type of Plant Polyphenol Extracted from Trapa bispinosa Inhibits Antibiotic Resistance of Drug-Resistant Staphylococcus aureus

“…Consequently, bacteria develop several adaptive mechanisms to eliminate the effects of antibacterial agents, including inactivating or excluding a drug and a structure conformation modification for bypassing the drug action [23]. Notably, the global spread and the increasing populations of antibiotic-resistant microbes are global public health concerns [4,24]. More than two million people are infected by antibiotic-resistant pathogens worldwide, resulting in over 700,000 deaths each year [24].…”

“…Based on a previous study, MIC values of TGII were determined for all S. aureus strains by using the twofold broth serial dilution method [4]. Briefly, S. aureus was diluted in MH broth and cultured overnight to achieve optimal cell density of nearly 2 × 10 6 cfu/mL (OD 600 = 0.01).…”

“…It is an important pathogen in both healthcare and community settings, and it causes opportunistic infections when the patient’s immune defense is compromised due to immune deficiency caused by catheter or ventilator use or surgery. [3,4]. Notably, bacteremia caused by S. aureus is a frequent concern in hospital-associated infections and accounts for approximately 20% of all cases of bloodstream infectious diseases, mainly resulting in high morbidity and mortality [5].…”

Triazole analogues as potential pharmacological agents: a brief review

“…The compound (2-(2,4-Dichlorophenyl)-3-(1H-indol-1-yl)-1-(1,2,4-1H-triazol-1-yl) propan-2-ol 1a exhibited the excellent activity against Candida, particularly against low fluconazole susceptible species. Result showed that this compound exhibited high activity as compared with fluconazole and similar to voriconazole against C. glabrata , C. krusei, and C. albicans [ 29 ].…”