Pinocembrin (PCB), a flavonoid known for its anti-inflammatory properties, has been approved for various clinical trial applications. To evaluate deeper into the anti-inflammatory potential of the specific enantiomer of natural PCB, we conducted the first investigation into the efficacy of the pure enantiomer (2S)-PCB in modulating inflammatory mediators induced by lipopolysaccharide (LPS) in both murine RAW 264.7 and human U937 macrophage cell lines. This particular compound was isolated from Goniothalamus macrophyllus (Annonaceae), a native plant of Indonesia. This plant has been used traditionally as an herbal medicine to alleviate inflammation. (2S)-PCB was isolated from the stem bark of G. macrophyllus by defatting with n-hexane followed by maceration with methanol. Purification was performed using several chromatographic techniques. The absolute configuration was determined using electronic circular dichroism (ECD) spectroscopy. This compound was then tested for its inhibitory activity on prostaglandin E2 (PGE2) and subjected to docking simulations. The results indicated that (2S)-PCB significantly suppressed the production of PGE2 induced by LPS in both RAW 264.7 and U937 cell lines. The docking simulations revealed that (2S)-PCB reduced PGE2 levels by suppressing mitogen-activated protein kinase (MAPK) activation through inhibiting p38 and extracellular signal-regulated kinases (ERK). These findings suggest that the compound may prevent worsening of septic shock caused by bacterial infection.
Aim: Chromones are promising for anticancer drug development.Methods & results: 12 chromone-based compounds were synthesized and tested against cancer cell lines. Compound 8 showed the highest cytotoxicity (LC50 3.2 μM) against colorectal cancer cells, surpassing 5-fluorouracil (LC50 4.2 μM). It suppressed colony formation, induced cell cycle arrest and triggered apoptotic cell death, confirmed by staining and apoptosis markers. Cell death was accompanied by enhanced reactive oxygen species formation and modulation of the autophagic machinery (autophagy marker light chain 3B (LC3B); adenosine monophosphate-activated protein kinase (AMPK); protein kinase B (PKB); UNC-51-like kinase (ULK)-1; and ULK2). Molecular docking and dynamic simulations revealed that compound 8 directly binds to ULK1.Conclusion: Compound 8 is a promising lead for autophagy-modulating anti-colon cancer drugs.
Monoamine oxidase (MAO) is crucial for the breakdown of monoamine neurotransmitters, making it a promising target for treating neurodegenerative disorders, such as depression, Alzheimer's disease, and Parkinson's disease. In this study, we investigated the selective inhibitory activity of chromone-based compounds against MAO-A and MAO-B for neurodegenerative disease treatment. In literary sources, thirty chromone derivatives have been identified as potential ligands for MAO-A and MAO-B inhibitors. We utilized molecular docking to evaluate how the most active compound interacted with the targeted MAO-A and MAO-B. Compound 2 g, the most active for MAO-A, demonstrated a lower CDOCKER energy compared to the co-crystallized ligand. Meanwhile, compound 2f, the most active for MAO-B, showed a CDOCKER energy similar to the co-crystallized ligand and exhibited similar binding patterns. Furthermore, we constructed a quantitative structure-activity relationship (QSAR) model to predict the properties and estimate IC50 values for 30 chromone derivatives functioning as MAO-A and MAO-B inhibitors. The model predictions were validated against experimental measurements. Our 2D QSAR model demonstrated robustness, with a statistically significant non-cross-validated coefficient (r2 < 0.9), cross-validated correlation coefficient (q2 < 0.6), and predictive squared correlation coefficient (r2pred < 0.8). Additionally, MD simulations confirmed the stable binding of compounds 2 g and 2f with MAO-A and MAO-B, respectively, displaying substantial binding energy. The most effective pharmacophore model identified key features, such as hydrogen bond acceptors and hydrophobic interactions, that contribute significantly to inhibitory potency. This study offers valuable insight into the selection of compounds with improved selectivity for MAO inhibition.