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We report the formulation, characterization, colloidal stability, and in vitro efficiency of Fisetin nanocrystals stabilized by poloxamer P407. Such nanocrystals present a nanometer scale (148.6 ± 1.1 nm) and a high homogeneity (polydispersity index of 0.17 ± 0.01), with a production yield of 97.0 ± 2.5%. The engineered formulations of nanocrystals suspension (pH of 7.4 ± 0.1), stabilized via steric repulsion, are stable for several days in aqueous environment (Milli Q water, NaCl 10 mM or mannitol 5% w/v), for few days in HEPES buffered saline (HBS) (20 / 150 mM) under sink conditions, and in culture medium. After freeze drying in 5% w/v mannitol, the nanocrystal formulations can be stored at −80 °C for at least 120 days. Drug release experiments displayed a 98.7 ± 5.1% cumulative release over 3 days in HBS. Compared to the free drug, the nanocrystal formulations showed an improved cytotoxicity highlighted by the decrease of the half maximal inhibitory concentration for both murine Lewis lung carcinoma (3LL) and human endothelial (EA.hy926) cell lines. In addition, after incubation with Fisetin nanosuspensions, significant changes in the cell morphology for both cell lines were observed, showing an improved anti-angiogenic effect of nanocrystals formulation compared to the free drug. Overall, Fisetin formulated as nanocrystals showed enhanced biopharmaceutical properties and in vitro activity, offering a wide range of indications for challenging applications in the clinic.

G-quadruplex DNAs (G4 DNAs) are emerging as promising anticancer drug targets due to their presence in the promoter regions of different oncogenes. Utilizing different spectroscopic techniques like UV–Vis absorption titration, thermal denaturation, spectrofluorimetric titration, fluorescence displacement assay, Job plot analysis, circular dichroism spectroscopy and also, molecular docking studies, the interaction of a synthetic nitro-flavone, 2-(4-Nitrophenyl)-4H-chromen-4-one (4NCO), with various G4 DNA structures (c-KIT1, c-KIT2, c-MYC, h-TELO and VEGF) was elucidated. We also investigated the effect of 4NCO on different cancer cell lines. Effect on cell morphology, DNA damage, cell cycle arrest, viability and mode of cell death were evaluated in A375 melanoma cells. Our findings indicated that 4NCO showed preferential binding towards c-MYC promoter G4 to stabilize it with a binding constant (Kb) value of the order of ~105 M−1 and binding stoichiometry of ~1:1. It also showed a unique dual binding mode when bound to c-MYC with a lower binding free energy having multiple strong interactions when compared to the other G4s. In cells, it induced DNA damage resulting in cell cycle arrest at G1/S phase until 24 h, after which, cells strictly underwent apoptosis. It also showed a preferential cytotoxicity towards the A375 melanoma cells. The ability of 4NCO to stabilize the c-MYC G4 to possibly suppress the over-expression of MYC was responsible for inhibition of proliferation of these cells. Hence, these results present a novel finding on the effectiveness of the nitro-flavone derivative 4NCO as a potent ligand for c-MYC G4 DNA thereby, providing possibilities of its use in cancer therapy for regulating the oncogene expression in cancer cells.

Quorum sensing (QS) is a cell-to-cell communication process that controls bacterial collective behaviors. The QS network regulates and coordinates bacterial virulence factor expression, antibiotic resistance and biofilm formation. Therefore, inhibition of the QS system is an effective strategy to suppress the bacterial virulence. Herein, we identify a phosphate ester derivative of chrysin as a potent QS inhibitor of the human pathogen Pseudomonas aeruginosa (P. aeruginosa) using a designed luciferase reporter assay. In vitro biochemical analysis shows that the chrysin derivative binds to the bacterial QS regulator LasR and abrogates its DNA-binding capability. In particular, the derivative exhibits higher anti-virulence activity compared to the parent molecule. All the results reveal the potential application of flavone derivative as an anti-virulence compound to combat the infectious diseases caused by P. aeruginosa.

In the title compound, C20H16O3, the hydropyran ring adopts a distorted half-chair conformation with the methine C atom and the ring O atom displaced by −0.554 (2) and 0.158 (1) Å, respectively, from the plane of the other four atoms (r.m.s. deviation = 0.020 Å). Its mean plane (all atoms) is inclined to the naphthalene ring system at a dihedral angle of 11.67 (1)°. The dihedral angle between the napthalene ring system and the phenyl ring is 71.84 (1)°. In the crystal, no diectional interactions beyond van der Waals contacts could be identified.

In the title molecule, C15H12O3, the C atoms bearing the hydroxy group and the phenyl ring are disordered over two sets of sites with refined occupancies of 0.573 (7) and 0.427 (7). There is also disorder of the phenyl ring but the hydroxy group was refined as ordered. The dihedral angles between the benzene ring of the chromane ring system and the phenyl ring are 89.7 (2)° for the major component of disorder and 72.1 (3)° for the minor component. Both disorder components of the the dihydropyran ring are in a half-chair conformation. In the crystal, molecules are linked by pairs of O—H...O hydrogen bonds, forming inversion dimers with an R22(10) graph-set motif. Weak C—H...π interactions link these dimers into ladders along [001].