Synthesis and antimicrobial activity of polyhalobenzonitrile quinazolin-4(3H)-one derivatives.

A novel series of polyhalobenzonitrile quinazolin-4(3H)-one derivatives were synthesized and characterized by NMR, IR, MS, and HRMS spectra. All of the newly prepared compounds were screened for antimicrobial activities against four strains of bacteria (Gram-positive bacterial: Staphylococcus aureus and Bacillus cereus; Gram-negative bacterial: Escherichia coli and Pseudomonas aeruginosa) and one strain of fungi (Candida albicans). Among the synthesized compounds, 5-(dimethylamino)-8-(2,4,5-trichloro-isophthalonitrile) quinazolin-4(3H)-one (7k) exhibited significant activity towards Gram-positive bacterial, Gram-negative bacterial, and the fungi strains. The MIC (0.8-3.3µg/mL) and MBC (2.6-7.8µg/mL) for this compound were close to those of nofloxacin, chlorothalonil, and fluconazole, making it the most potent antimicrobial agents in the series.

Tautomeric-Dependent Lactam Cycloaddition with Nitrile Oxide: Facile Synthesis of 1,2,4-Oxadiazole[4,5-a]indolone Derivatives.

A concise, metal-free, and gram-scale strategy to convert indoline-2,3-diones to 1,2,4-oxadiazole[4,5-a]indolones through an improved [3 + 2] cycloaddition of α-ketone-lactam with nitrile oxides has been developed. The lactim form of the resonance structure of isatin in protic solvents is the key active dipolarophile that shows chemo- and regioselectivity under experimental and theoretical conditions. This strategy conveniently enabled the assembly of several 1,2,4-oxadiazole[4,5-a]indolines with a broad range of functional groups. Compounds 3a and 4b exhibit cytotoxicity in the NCI/ADR-RES, SKOV3, and OVCAR8 cell lines.

Preparation, spectroscopy and molecular modelling studies of the inclusion complex of cordycepin with cyclodextrins.

The inclusion complexes of cordycepin with cyclodextrins (CDs) were prepared, the resultant complexes were characterised by UV-vis, FTIR, DSC, SEM, XRD, ESI-MS and proton nuclear magnetic resonance spectroscopy ((1)H NMR). The stoichiometry was established using a Job plot and the inclusion mechanism was clarified using molecular dynamic simulations. Molecular modelling calculations have been carried out to rationalise the experimental findings and predict the stable molecular structure of the inclusion complex. The stability of the inclusion complexes were confirmed by energetic and thermodynamic properties (ΔE, ΔH, ΔG and ΔS) and HOMO, LUMO orbital. The 1:1 binding model of complexes were visually proved by ESI-MS experiment. Our results showed that the purine group of cordycepin molecule was deeply inserted into the cavity of CDs.

Novel water-soluble fisetin/cyclodextrins inclusion complexes: Preparation, characterization, molecular docking and bioavailability.

Novel water-soluble inclusion complexes for fisetin (FIT) were developed by introducing ß-cyclodextrin (ß-CD) and γ-CD. Properties of the obtained complexes, as well as the interactions between each component, were systematically investigated in both solution and solid states by means of ESI-MS, NMR, FT-IR, XRD, DSC, SEM etc. All characterization information demonstrated that FIT/CDs inclusion complexes were formed, and exhibited different spectroscopic features and properties from FIT. A complex with 1:1 stoichiometry of FIT and CDs was confirmed with Job's method. Meanwhile, as supported by molecular modeling calculations, we suggested that phenyl group (C ring) of FIT molecule was included in the CDs cavity from the wide side. Moreover, the water solubility of FIT/CDs was successfully improved from 2.8 mg/mL (in ethanol aqueous solution) to 4.5 mg/mL (FIT/ß-CD complex) and 7.8 mg/mL (FIT/γ-CD complex), and higher thermal stability results were shown by thermal analysis for those complexes. Notably, the inclusion complexes displayed almost two times higher cytotoxicity compared to free FIT against Hela and MCF-7 cells. These results suggested that FIT/CDs complexes could be potentially useful in food industry and healthcare area.

Synthesis and In-Vitro Cytotoxicity of (E)-N,2,3-Triarylacrylamide Derivatives as Analogs of Combretastatin A-4.

A new series of (E)-N,2,3-triarylacrylamide derivatives were designed and synthesized as potent anticancer agents. Cytotoxicity of the 26 target compounds was evaluated in vitro against six cancer cell lines (HCT116, A549, MDA-MB-468, HepG2, SKNMC and SK-OV-3) by Sulforhodamine B colorimetric assay. The most promising compound, 4h, was as potent as the reference drug cisplatin (DDP). Preliminary structure-activity relationship (SAR) data provided guidance for further design and discovery of (E)- N,2,3-triarylacrylamide scaffold anticancer agents.

Investigation of inclusion complex of epothilone A with cyclodextrins.

The inclusion complexation of Epothilone A with native cyclodextrin (ß- or γ-CD) and its derivative hydroxypropyl-ß-cyclodextrin (HPßCD) were prepared. Their behavior, characterization, and binding ability were investigated in both solution and the solid state by means of UV-vis, NMR, XRD, DSC and SEM. The results show that the water solubility and solution stability obviously increased in the inclusion complex with cyclodextrins. Meanwhile, the inclusion complexes still retained anticancer activity against A549 and MCF-7 cells, similar to free Epothilone A. This satisfactory water solubility, high solution stability, and high anticancer activity of the Epothilone A/CD complexes will be potentially useful as an anticancer therapy.