Synthesis of chalcones and their antimicrobial and drug potentiating activities

• Published in: Microbial pathogenesis 2023-07, Vol.180, p.106129-106129, Article 106129
• Main Authors: dos Santos, Antonia Thassya Lucas, de Araújo-Neto, José Bezerra, Costa da Silva, Maria Milene, Paulino da Silva, Maria Elenilda, Carneiro, Joara Nályda Pereira, Fonseca, Victor Juno Alencar, Coutinho, Henrique Douglas Melo, Bandeira, Paulo Nogueira, dos Santos, Hélcio Silva, da Silva Mendes, Francisco Rogênio, Sales, Débora Lima, Morais-Braga, Maria Flaviana Bezerra
• Format: Article
• Language: English
• Subjects: Antibacterial; Antifungal; Candida albicans; Candida tropicalis; chalcones; chemical structure; condensation reactions; Drugs; Escherichia coli; fluconazole; fungi; gas chromatography; gentamicin; mass spectrometry; minimum inhibitory concentration; norfloxacin; nuclear magnetic resonance spectroscopy; pathogenesis; penicillins; Pseudomonas aeruginosa; Resistance; Staphylococcus aureus
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2023.106129

The increased resistance of microorganisms to antimicrobial drugs makes it necessary to search for new active compounds, such as chalcones. Their simple chemical structure makes them molecules easy to synthesize. Therefore, the aim of this study was to evaluate the antimicrobial and potentiating activity of antibiotics and antifungals by synthetic chalcones against strains of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Candida tropicalis. The synthesis of chalcones was carried out by Claisen-Schimidt aldol condensation. Nuclear Magnetic Resonance (NMR) and Gas Chromatography Coupled to Mass Spectrometry (GC/MS) were also performed. Microbiological tests were performed by the broth microdilution method, using gentamicin, norfloxacin and penicillin as standard drugs for the antibacterial assay, and fluconazole for the antifungal assay. Three chalcones were obtained (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one (DB-Acetone), (1E,3E,6E,8E)-1,9-diphenylnone-1,3,6,8-tetraen-5-one (DB-CNM), (1E,4E)-1,5-bis (4-methoxyphenyl) penta-1,4-dien-3-one (DB-Anisal). The compound DB-Acetone was able to inhibit P. aeruginosa ATCC 9027 at a concentration of 1.4 × 102 μM (32 μg/mL), while DB-CNM and DB-Anisal inhibited the growth of S. aureus ATCC 25923 at 17.88 × 102 μM and 2.71 × 101 μM (512 μg/mL and 8 μg/mL) respectively. In the combined activity, DB-Anisal was able to potentiate the effect of the three antibacterial drugs tested against E. coli 06, norfloxacin (128 for 4 μg/mL ±1) against P. aeruginosa 24 and penicillin (1,024 for 16 μg/mL ±1) against S. aureus 10. In antifungal assays, chalcones were not able to inhibit the growth of fungal strains tested. However, both showed potentiating activity with fluconazole, ranging from 8.17 x 10−1 μM (0.4909 μg/mL) to 2.35 μM (13.96 μg/mL). It is concluded that synthetic chalcones have antimicrobial potential, demonstrating good intrinsic activity against fungi and bacteria, in addition to potentiating the antibiotics and antifungal tested. Further studies are needed addressing the mechanisms of action responsible for the results found in this work. •DB – Acetone had an intrinsic effect on P. aeruginosa ATCC 9027.•DB – CNM and DB – Anisal inhibited S. aureus ATCC 25923.•Chalcones reduced the fungal population at a concentration of 512 μg/mL.•Chalcones demonstrated an antibiotic and antifungal potentiating activity.