Novel O-alkyl Derivatives of Naringenin and Their Oximes with Antimicrobial and Anticancer Activity

Abstract

In our investigation, we concentrated on naringenin (NG)—a widely studied flavanone that occurs in citrus fruits. As a result of a reaction with a range of alkyl iodides, 7 novel O-alkyl derivatives of naringenin (7a–11a, 13a, 17a) were obtained. Another chemical modification led to 9 oximes of O-alkyl naringenin derivatives (7b–13b, 16b–17b) that were never described before. The obtained compounds were evaluated for their potential antibacterial activity against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. The results were reported as the standard minimal inhibitory concentration (MIC) values and compared with naringenin and its known O-alkyl derivatives. Compounds 4a, 10a, 12a, 14a, 4b, 10b, 11b, and 14b were described with MIC of 25 µg/mL or lower. The strongest bacteriostatic activity was observed for 7-O-butylnaringenin (12a) against S. aureus (MIC = 6.25 µg/mL). Moreover, the antitumor effect of flavonoids was examined on human colon cancer cell line HT-29. Twenty-six compounds were characterized as possessing an antiproliferative activity stronger than that of naringenin. The replacement of the carbonyl group with an oxime moiety significantly increased the anticancer properties. The IC50 values below 5 µg/mL were demonstrated for four oxime derivatives (8b, 11b, 13b and 16b).

Antimicrobial O-Alkyl Derivatives of Naringenin and Their Oximes Against Multidrug-Resistant Bacteria

“…For the group of 18 compounds tested against priority pathogens, we have chosen 14 O -alkyl derivatives of naringenin and their oximes whose bacteriostatic activity against the non-MDR reference strains of bacteria has been proved in a previous work by Kozłowska et al [ 32 ].…”

“…Our previous studies did not show an unambiguous relationship between the length of the aliphatic chain and antimicrobial activity [ 32 ]. Therefore, the extension of our library by compounds that have not been described yet and the presentation of their biological activity is interesting and constitutes a novelty within the framework of this research.…”

“…In the previous work by Kozłowska et al [ 32 ], the structure and biological activity of seven novel O -alkyl derivatives of naringenin ( 1a – 7a ) and seven of their oximes ( 1b – 7b ) were demonstrated. They were tested against reference strains of E. coli, S. aureus, and B. subtilis from the American Type Culture Collection (ATCC).…”

On the Physicochemical Characteristics and Applications of an “Undesirable” Pyrenean Thorny Cushion Dwarf: Echinospartum horridum (Vahl) Roth

“…For the identification of the various compounds present in the extract, the high-resolution mass spectrum was measured on a Maxis Impact spectrometer (Bruker Daltonik GmbH, Bremen, Germany) using direct infusion ESI Q-TOF MS. The spectrometer was operated in linear positive mode in the m/z range of 50–600 Da, under the following conditions: 3.5 kV potential between spray needle and orifice, 0.4 bar nebulizer pressure, 3.0 L·min −1 drying gas flow rate at 200 °C, and 3.0 µL·min −1 sample flow rate [ 38 ]. The analysis was outsourced at the Laboratorio de Técnicas Instrumentales facilities of Universidad de Valladolid.…”

Less Cytotoxic Protoflavones as Antiviral Agents: Protoapigenone 1′-O-isopropyl ether Shows Improved Selectivity Against the Epstein–Barr Virus Lytic Cycle

“…Several studies underline that the preparation of flavonoid oxime derivatives can be a simple yet effective synthetic option for enhancing certain biological effects of the parent compound, e.g., antimicrobial [22], antioxidant [23], and antitumor [24] properties. Compounds with different B-ring saturation and/or 1 -O-substituents (6-9 and 14) were selected for the preparation of 4 -oximes to further increase chemical and consequential pharmacological diversity (Scheme 1).…”