Ultrasound‐assisted facile synthesis of Boron‐Heck‐coupled sclareol analogues as potential antibacterial agents against Staphylococcus aureus

摘要

Abstract Aim To evaluate the antimicrobial capability of sclareol and its derivatives against Staphylococcus aureus and its Methicillin‐resistant strain (MRSA). Methods and Results. A new series of Boron‐Heck‐coupled sclareol analogues were prepared by structural modifications at the C‐15 terminal double bond of sclareol using ultrasonication. The structural modifications were designed to keep the stereochemistry of all the five chiral centres of sclareol intact. A two‐step reaction scheme consisting of Boron‐Heck coupling of sclareol followed by Wittig reaction was carried out to produce novel sclareol congeners for antimicrobial evaluation. Three compounds SAJ‐1, SAJ‐2 and SB‐11 exhibited strong antibacterial activity against S. aureus and Methicillin‐resistant strain (MRSA) with MIC values between 3 and 11 μM. Among all the screened compounds, SAJ‐1 and SAJ‐2 showed the best antibiofilm profiles against both strains. Moreover, SAJ‐1 and SAJ‐2 acted synergistically with streptomycin against S. aureus while creating varying outcomes in combination with ciprofloxacin, penicillin and ampicillin. SAJ‐1 also acted synergistically with ampicillin against S. aureus, while SB‐11 showed synergism with ciprofloxacin against both pathogens. Moreover, SAJ‐1 and SAJ‐2 also inhibited staphyloxanthin production in S. aureus and MRSA and induced postantibiotic effects against both pathogens. Conclusions It can be inferred that SAJ‐1, SAJ‐2 and SB‐11 may act as potential chemical entities for the development of antibacterial substances. The study revealed that SAJ‐1 and SAJ‐2 are the most suitable sclareol analogues for further studies towards the development of antibacterial substances. Significance and Impact of the Study SAJ‐1, SAJ‐2 and SB‐11 show promising antibacterial properties against Staphylococcus aureus. Efforts should be made and more research should be done utilizing in vivo models to determine their efficacy as antibiotics.