Cytotoxicity and Anti-inflammatory Properties of Apigenin-Derived Isolaxifolin

Abstract

The rare flavonoid isolaxifolin, a potent insecticide, has been touted as a potential grain-protecting agent. In order to assess any impact of this natural product on human health and to explore its various other biological properties, we have established a semisynthesis from the simpler but structurally related and more abundant natural product apigenin. The five-step reaction sequence has provided, for the first time, sufficient material for an indepth evaluation of the cytotoxic properties of the title natural product. The impact of isolaxifolin on certain pro-inflammatory cytokines in murine macrophage RAW 264.7 cells has also been examined. Such studies have revealed that isolaxifolin displays no toxic effects toward normal cells while displaying greater cytotoxicities against certain cancer cell lines than its synthetic precursor apigenin. Furthermore, unlike apigenin, isolaxifolin only reduced NO, TNF-α, and IL-6 secretions in LPS-induced RAW 264.7 cells in a rather modest and dose-independent manner.

Total Synthesis and Antibacterial Evaluation of Lupinifolin and Its Natural Analogues

“…The organic layers were combined, dried over Na 2 SO 4 , and evaporated. The residue obtained was purified over flash column chromatography with PE/EtOAc (50: (26) mmol), 3 Å powdered molecular sieves (500 mg), and Pd(PPh 3 ) 4 (93 mg, 0.08 mmol, 10 mol %) in dry degassed THF (10 mL) was added compound 24 (2.20 g, 12.00 mmol, 15 equiv) at 0 °C. The mixture was stirred at 0 °C for 18 h. After the reaction was completed (detected by TLC), the solvents were removed in vacuo.…”

“…Then the −MOM protecting groups at C-4 and C-6 of 9a were removed by treatment with a diluted HCl solution to generate 10a (88%) . Compound 10a was subsequently treated with 3-methyl-2-butenal ( 11 ) in the presence of Ca­(OH) 2 to obtain 6,7-pyran adduct 12a (45%). − It is worth mentioning that only the 6,7-pyran product was obtained, while the corresponding 7,8-cyclized product was not detected despite the apparent similarity of the two positions. Compound 12a was coupled with 3-methylbut-2-en-1-ol ( 13 ) under the classical Mitsunobu conditions (diethyl azodicarboxylate (DEAD), triphenylphosphine [P­(Ph) 3 ] in dry tetrahydrofuran (THF)) to give 5-prenyl ether 14 .…”

Perplexing Polyphenolics: The Isolations, Syntheses, Reappraisals, and Bioactivities of Flavonoids, Isoflavonoids, and Neoflavonoids from 2016 to 2022

“…The latter was treated with acetic anhydride in the presence of pyridine and subsequently condensed with 3-methyl-2-buten-1-ol under Mitsunobu conditions using triphenylphosphine and diethyl azodicarboxylate to give compound 378 . A europium(III)-tris(1,1,1,2,2,3,3-heptafluoro-7,7-dimethyl-4,6-octanediotnae-catalyzed tandem para-Claisen–Cope rearrangement of compound 378 yielded compound 379 , which was hydrolyzed to isolaxifolin ( 380 ) [ 98 ].…”

“…It arrested cells at the G 0 /G 1 phase and disrupted the mitochondrial membrane potential (MMP) in MDA-MB-231 cells. Additionally, it did not potently inhibit NO generation in LPS-induced RAW 264.7 cells [ 98 ].…”