Effects of substituent pattern on the intracellular target of antiproliferative benzo[b]thiophenyl chromone derivatives

Three new and rare chromone derivatives, epiremisporine C (1), epiremisporine D (2), and epiremisporine E (3), were isolated from marine-derived Penicillium citrinum, together with four known compounds, epiremisporine B (4), penicitrinone A (5), 8-hydroxy-1-methoxycarbonyl-6-methylxanthone (6), and isoconiochaetone C (7). Among the isolated compounds, compounds 2–5 significantly decreased fMLP-induced superoxide anion generation by human neutrophils, with IC50 values of 6.39 ± 0.40, 8.28 ± 0.29, 3.62 ± 0.61, and 2.67 ± 0.10 μM, respectively. Compounds 3 and 4 exhibited cytotoxic activities with IC50 values of 43.82 ± 6.33 and 32.29 ± 4.83 μM, respectively, against non-small lung cancer cell (A549), and Western blot assay confirmed that compounds 3 and 4 markedly induced apoptosis of A549 cells, through Bcl-2, Bax, and caspase 3 signaling cascades.

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Chromene and chromone derivatives as liver X receptors modulators from a marine-derived Pestalotiopsis neglecta fungus

Bioorganic Chemistry ◽

10.1016/j.bioorg.2021.104927 ◽

2021 ◽

pp. 104927

Author(s):

Zhi Liang ◽

Tanwei Gu ◽

Jianjiao Wang ◽

Jianglian She ◽

Yuxiu Ye ◽

...

Keyword(s):

Liver X Receptors ◽

Chromone Derivatives ◽

X Receptors ◽

Pestalotiopsis Neglecta

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Insights into the Action Mechanism of the Antimicrobial Peptide Lasioglossin III

International Journal of Molecular Sciences ◽

10.3390/ijms22062857 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2857

Author(s):

Filomena Battista ◽

Rosario Oliva ◽

Pompea Del Vecchio ◽

Roland Winter ◽

Luigi Petraccone

Keyword(s):

Antimicrobial Peptide ◽

Gram Negative Bacteria ◽

Lipid Domains ◽

Action Mechanism ◽

Cationic Antimicrobial Peptide ◽

Intracellular Targeting ◽

Gel Retardation Assay ◽

Charged Membrane ◽

Intracellular Target ◽

Anionic Lipids

Lasioglossin III (LL-III) is a cationic antimicrobial peptide derived from the venom of the eusocial bee Lasioglossum laticeps. LL-III is extremely toxic to both Gram-positive and Gram-negative bacteria, and it exhibits antifungal as well as antitumor activity. Moreover, it shows low hemolytic activity, and it has almost no toxic effects on eukaryotic cells. However, the molecular basis of the LL-III mechanism of action is still unclear. In this study, we characterized by means of calorimetric (DSC) and spectroscopic (CD, fluorescence) techniques its interaction with liposomes composed of a mixture of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-rac-phosphoglycerol (POPG) lipids as a model of the negatively charged membrane of pathogens. For comparison, the interaction of LL-III with the uncharged POPC liposomes was also studied. Our data showed that LL-III preferentially interacted with anionic lipids in the POPC/POPG liposomes and induces the formation of lipid domains. Furthermore, the leakage experiments showed that the peptide could permeabilize the membrane. Interestingly, our DSC results showed that the peptide-membrane interaction occurs in a non-disruptive manner, indicating an intracellular targeting mode of action for this peptide. Consistent with this hypothesis, our gel-retardation assay experiments showed that LL-III could interact with plasmid DNA, suggesting a possible intracellular target.

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