Ultrasound Assisted Synthesis, Characterization and Antimicrobial Evaluation of Novel Oxazolidinone- Biphenyl Chalcone Hybrid Derivatives

Abstract

Objective:The main objective of our present study, is to potentiate the antibacterial activity of biphenyl chalcones and oxazolidinones, thus in order to achieve the potent antibacterial agents, we coupled both derivatives by using green chemistry approach for Buchwald's protocol under ultrasound irradiation. Methodology: Ultrasonication technique was used to couple a series of 24 novel bromo-biphenyl-chalcone derivatives and 5-chloromethyl-oxazolidinone in the presence of copper iodide (CuI) (10 mol %) for the amidation of chalcones and (±)-trans-1,2-diaminocyclohexane was used to solubilize CuI and potassium carbonate (K 2 CO 3 ) as base, which provided the products in good yields after short reaction times under mild conditions. Results and Discussion: Herewith we report the synthesis of 24 novel oxazolidinone-biphenyl chalcone hybrid derivatives (7a-7x). All the synthesized compounds were characterized by spectral data and evaluated for in vitro antibacterial and antifungal activities. Antibacterial and antifungal activities were tested using the serial dilution method. From the screening studies it was observed that compounds 7c to 7g have shown significant antibacterial activities against the both the strains of gram-positive and gram-negative bacteria at 3.125 µg/ml when compared to the standard drugs ciprofloxacin and linezolid and were as other compounds showed moderate to weak activities. In case of antifungal studies the compounds 7e-7g showed moderate activities at 12.5 µg/ml compared to standard fluconazole and whereas other compounds showed weak activities. Conclusion: We have developed an experimentally simple, efficient, short time and high yielding CuI-mediated N-arylation of oxazolidinones under ultrasound irradiation with a simple set up at room temperature. This approach would be a worthwhile in the development of green chemistry protocols. Compounds 7c to 7g have shown significant antibacterial activities against the both the strains of gram-positive and gram-negative bacteria.

Current Landscape and Future Perspective of Oxazolidinone Scaffolds Containing Antibacterial Drugs

“…Panigrahi et al coupled oxazolidinone and a biphenyl chalcone, which both have strong antibacterial activity, by using a green chemistry approach for Buchwald’s protocol under ultrasound irradiation and obtained a series of novel oxazolidinone–biphenyl chalcone hybrid derivatives (Figure ). In vitro antibacterial and antifungal activity studies showed that compared with the standard drugs ciprofloxacin and linezolid, compounds 7a – i showed significant antibacterial activity against both Gram-positive bacteria ( S. aureus , Bacillus subtilis ( B. subtilis ), and Streptococcus faecalis ( S. faecalis )) and Gram-negative bacteria ( Escherichia coli ( E. coli ), Klebsiella pneumoniae ( K. pneumoniae ), and Pseudomonas aeruginosa ( P. aeruginosa )) (MIC: 3.125–6.25 μg/mL). In the case of antifungal studies, compared with fluconazole (MIC: 6.25 μg/L against Candida albicans ( C. albicans ) and Aspergillus niger ( A. niger )), 7c – e exhibited medium potency against A. niger and C. albicans (MIC: 12.5 μg/mL).…”

“…Panigrahi et al coupled oxazolidinone and a biphenyl chalcone, which both have strong antibacterial activity, by using a green chemistry approach for Buchwald's protocol under ultrasound irradiation and obtained a series of novel oxazolidinone−biphenyl chalcone hybrid derivatives (Figure 7). 59 In vitro antibacterial and antifungal activity studies showed that compared with the standard drugs ciprofloxacin and linezolid, compounds 7a−i showed significant antibacterial activity against both Gram-positive bacteria (S. A systematic SAR study on screened compounds revealed that the effects of substitutions on ring R on the antibacterial potency were mainly steric; only the small or linear substituents (F < Cl < NO 2 OH < CH 3 < OCH 3 ) could be tolerated by the ribosomal binding site, whereas increases in the bulk of substituents were not tolerated. The results of this study may be able to guide researchers to further modify novel oxazolidinone−biphenyl chalcone hybrid derivatives and design more effective and selective antibacterial and antifungal agents.…”

Biological Role of Chalcones in Medicinal Chemistry

“…Oxazolidinones incorporated with chalcone hybrids (12) were evaluated for in vitro antibacterial and antifungal activities by using the serial dilution method [16]. Results showed moderate antimicrobial activities as compared with the standard drugs ciprofloxacin and linezolid.…”