New flavonoid glycosides conjugates: synthesis, characterization, and evaluationof their cytotoxic activities

Abstract

A series of novel halogenated 3-hydroxyflavones (3HFs) were prepared by reacting halogenated hydroxyacetophenones with the appropriate aromatic aldehyde. Glycosylation of 3HFs with acetobromoglucose and deprotection of the acetyl protective groups afforded the desired 3-O -flavonoids glycosides in satisfactory yields. All the prepared compounds were tested for their cytotoxic activity against HCT-116, MCF-7, and OVCAR-3 human cancer cell lines.The 3HFs exhibited higher cytotoxic activities compared with the glycosylated flavonoids. Overall, the structure-activity relationship study showed that the introduction of glycoside moiety at the C-3 OH position does not improve the bioactivity.Recent interest in the O -glycoside and/or C -glycoside forms has been stimulated by the potential health benefits arising from the hugely diverse bioactivities of these flavonoid derivatives. The specific properties of these flavonoid derivatives might be due to the presence of aromatic and glycoside moieties and many hydroxyl groups. However, the dietary flavonoid C -glycosides have received less attention than their corresponding O -glycosides. 7 Among the flavonoid derivatives of pharmacological and biological interest, the 3-hydroxyflavones (3HFs) or flavonols constitute a major class as they are endowed with various biological activities such as antiinflammatory, 8 antiacetylcholinesterase, 9 antioxidant, 10,11 anticancer, 12,13 antidepressant, 14,15 antidiabetic, 16 antimicrobial, 17 antihypertensive, 18 anti-HIV, 19 and antiallergic. 20 On the other hand, it has been found that almost all the dietary flavonoids, especially flavonols, exist in nature as α -or β -glycoside forms such as flavonoid glucosides, rhamnosides, galactosides, arabinosides, and rutinosides. 3,21 As a special type of flavonoid O -glycoside, flavonol * Correspondence: hichem.bjannet@gmail.com This work is licensed under a Creative Commons Attribution 4.0 International License.O -glycosides are often found in nature and so far more than 1500 of them have been isolated and characterized, mostly from higher plants, 22 and the majority of these compounds ( ∼80%) have a sugar linkage at the 3-OH.Moreover, flavonol O -glycosides have been proven to have promising pharmaceutical activities. 23 The high rate of occurrence and the importance of flavonol glycosides have attracted attention to synthetic studies of this group of natural products.It was further reported that natural flavonols are frequently substituted at variable positions, mainly by hydroxyl, methoxyl, isoprenyl, and glycosyl groups, and it was also thought that biological activities of flavonols are due to the presence of these substituents. 24 Nevertheless, it has been demonstrated that halogenated organic derivatives also exhibit significant biological activities. 25Since halogenated substituted flavonols are not found in nature and since glycosylation of flavonoids improves their solubility, stability, and bioavailability relative to flavonoid aglycones, and as a part of our general program in ...

Hydrazide‐Bridged Pyridazines for Cholinesterase Inhibitors: Synthesis, Characterizations, In Silico, and In Vitro Evaluation

“…After 24 h, cells were washed with Phosphate‐buffered saline (PBS) solution three and incubated with 0.5 mg/mL MTT solution in serum‐free culture medium at 37 °C, 5 % CO 2 for 2–4 h. Then, the formed formazan crystals were dissolved in the DMSO (dimethyl sulfoxide), and the solutions were UV‐Vis spectroscopic measured at 570 nm using a microplate reader. The percentage of cell inhibition is calculated based on Equation 2 [33–35] . $$$\vcenter{\openup.5em\halign{$\displaystyle{#}$\cr {\bf \char37 \ C e l l \ V i a b i l i t y}=[({\rm A}{_{{\rm sample}}}- {\rm A}{_{{\rm blank}}})/{\rm A}{_{{\rm live}}}- {\rm A}{_{{\rm blank}}})]\times 100\hfill\cr}}$$$ …”

“…The percentage of cell inhibition is calculated based on Equation 2. [33][34][35] % Cell Viability ¼ ½ðA sample À A blank Þ=A live À A blank Þ� � 100…”