Natural-derived acetophenones: chemistry and pharmacological activities

Acetophenones, which show scattered distribution in organisms including phylogenetically distant plants and fungi, are play diverse roles in plant-plant, plant-insect, plant-microbiome, and even animal-insect interactions. However, the enzymes involved in plant acetophenone biosynthetic pathway remain enigmatic. Here we uncover the complete biosynthesis pathway of 4-hydroxyacetophenone glucoside using pear as a model organism. We demonstrate that the natural occurrence of 4-hydroxyacetophenone in certain pear cultivars is due to the impaired shortening reaction of propanoid side chain of 4-hydroxy-3-oxo-3-phenylpropanoyl CoA. This reaction is catalyzed by a peroxisomal 3-ketoacyl-CoA thiolase, which is homozygous malfunctioning in these pear cultivars. This rare phenomenon reminds us that not only neofunctionalization but ‘malfunctionalization’ also fuels diversification in plant secondary metabolism. Forward genetic approaches are powerful to shed light on such ‘hidden’ or recessive pathways in plants.

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Enzyme (α-Glucosidase, α-Amylase, PTP1B & VEGFR-2) Inhibition and Cytotoxicity of Fluorinated Benzenesulfonic Ester Derivatives of the 5-Substituted 2-Hydroxy-3-nitroacetophenones

Olomola,

Nkoana,

et al. 2024

IJMS

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The prevalence of small multi-target drugs containing a fluorinated aromatic moiety among approved drugs in the market is due to the unique properties of this halogen atom. With the aim to develop potent antidiabetic agents, a series of phenylsulfonic esters based on the conjugation of the 5-substituted 2-hydroxy-3-nitroacetophenones 1a–d with phenylsulfonyl chloride derivatives substituted with a fluorine atom or fluorine-containing (-CF3 or -OCF3) group were prepared. Their structures were characterized using a combination of spectroscopic techniques complemented with a single-crystal X-ray diffraction (XRD) analysis on a representative example. The compounds were, in turn, assayed for inhibitory effect against α-glucosidase, α-amylase, protein tyrosine phosphatase 1 B (PTP1B) and the vascular endothelial growth factor receptor-2 (VEGFR-2) all of which are associated with the pathogenesis and progression of type 2 diabetes mellitus (T2DM). The antigrowth effect of selected compounds was evaluated on the human breast (MCF-7) and lung (A549) cancer cell lines. The compounds were also evaluated for cytotoxicity against the African Green Monkey kidney (Vero) cell line. The results of an in vitro enzymatic study were augmented by molecular docking (in silico) analysis. Their ADME (absorption, distribution, metabolism and excretion) properties have been evaluated on the most active compounds against α-glucosidase and/or α-amylase to predict their drug likeness.

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Natural-derived acetophenones: chemistry and pharmacological activities

Cited by 5 publications

References 148 publications

New acetophenone scaffolds: Synthesis, antifungal activities, biocompatibility, molecular docking, ADMET analysis and dynamic simulations

New acetophenone scaffolds: Synthesis, antifungal activities, biocompatibility, molecular docking, ADMET analysis and dynamic simulations

Natural impaired peroxisomal side-chain shortening reaction of 3-oxo-3-phenylpropanoyl CoA reveals plant acetophenone biosynthetic pathway

Enzyme (α-Glucosidase, α-Amylase, PTP1B & VEGFR-2) Inhibition and Cytotoxicity of Fluorinated Benzenesulfonic Ester Derivatives of the 5-Substituted 2-Hydroxy-3-nitroacetophenones

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