Nitrogen‐containing flavonoid and their analogs with diverse B‐ring in acetylcholinesterase and butyrylcholinesterase inhibition

Abstract

In this study, a series of new flavones (2-phenyl-chromone), 2-naphthyl chromone, 2-anthryl-chromone, or 2-biphenyl-chromone derivatives containing 6 or 7-substituted tertiary amine side chain were designed, synthesized, and evaluated in acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition. The results indicated that the alteration of aromatic ring connecting to chromone scaffold brings about a significant impact on biological activity. Compared with flavones, the inhibitory activity of 2-naphthyl chromone, 2-anthryl-chromone derivatives against AChE significantly decreased, while that of 2-biphenyl chromone derivatives with 7-substituted tertiary amine side chain is better than relative flavones derivatives. For all new synthesized compounds, the position of tertiary amine side chain obviously influenced the activity of inhibiting AChE. The results above provide great worthy information for the further development of new AChE inhibitors. Among the newly synthesized compounds, compound 5a is potent in AChE inhibition (IC 50 = 1.29 ± 0.10 μmol/L) with high selectivity for AChE over BChE (selectivity ratio: 27.96). An enzyme kinetic study of compound 5a suggests that it produces a mixed-type inhibitory effect against AChE.

A Small Molecule That Promotes Cellular Senescence Prevents Fibrogenesis and Tumorigenesis

“…Due to the fact of their anti-oxidant or anti-inflammatory potential, flavones have long been used to treat inflammatory diseases such as arthritis and asthma [ 11 ]. Chromone, 1,4-benzopyrone-4-one, is a central chemical scaffold that is found in flavones and isoflavones [ 12 ]. We recently reported that eupatilin, a CS-containing compound isolated from an Artemisia species, and its synthetic analog ONG41008 inhibit fibrogenesis in vitro and fibrosis in vivo.…”

Divergent Total Synthesis of Fornicin A, Fornicin D, and Ganodercin D, Meroterpenoids from Ganoderma Mushrooms

“…To install the two THP groups on 2,5-dihydroxyacetophenone, we followed a literature procedure, using an excess of 3,4-DHP and catalytic PPTS in DCM. [12][13][14][15][16][17][18][19] Although the preparation of the bis-THP-protected product 10 has been reported several times by different groups, surprisingly, no NMR or MS spectra of 10 are available. With the reported procedures, we obtained the mono-THP-protected product 9 instead, and only trace amounts of 10.…”

Inhibitory potential of nitrogen, oxygen and sulfur containing heterocyclic scaffolds against acetylcholinesterase and butyrylcholinesterase

“…Compared with flavones, the inhibitory activity of 2-naphthyl chromone, 2-anthryl-chromone derivatives against AChE significantly decreased, while that of 2-biphenyl chromone derivatives with 7-substituted tertiary amine side chain is better than relative flavones derivatives. Among the newly synthesized compounds, compound 313 was potent in AChE inhibition (IC 50 = 1.29 µmol L −1 ) with high selectivity for AChE over BChE (selectivity ratio: 27.96) 290 ( Table 15 ).…”