Synthesis, telomerase inhibitory and anticancer activity of new 2-phenyl-4H-chromone derivatives containing 1,3,4-oxadiazole moiety

Abstract

Based on previous studies, 66 2-phenyl-4H-chromone derivatives containing amide and 1,3,4-oxadiazole moieties were prepared as potential telomerase inhibitors. The results showed most of the title compounds exhibited significantly inhibitory activity on telomerase. Among them, some compounds demonstrated the most potent telomerase inhibitory activity (IC 50 < 1 mM), which was significantly superior to the staurosporine (IC 50 ¼ 6.41 mM). In addition, clear structure-activity relationships were summarised, indicating that the substitution of the methoxy group and the position, type and number of the substituents on the phenyl ring had significant effects on telomerase activity. Among them, compound A33 showed considerable inhibition against telomerase. Flow cytometric analysis showed that compound A33 could arrest MGC-803 cell cycle at G2/M phase and induce apoptosis in a concentration-dependent way. Meanwhile, Western blotting revealed that this compound could reduce the expression of dyskerin, which is a fragment of telomerase.

1,3,4-Oxadiazole Derivatives as Plant Activators for Controlling Plant Viral Diseases: Preparation and Assessment of the Effect of Auxiliaries

“…Instruments and Chemicals. NMR spectra (e.g., 1 H NMR, 13 C NMR, and 19 F NMR) of all compounds were verified by operating a JEOL-ECX-500 or Bruker Biospin AG-400 instrument with the CDCl 3 solvent containing the internal standard tetramethylsilane (TMS). High-resolution mass spectrometry (HRMS) data were performed on an LTQ Orbitrap (Thermo Scientific, Missouri, USA).…”

“…For example, approximately 60% of existing agrochemicals possess at least one heterocyclic ring. , Therefore, introducing a heterocyclic skeleton may be useful to develop novel agrochemicals. Notably, the 1,3,4-oxadiazole framework, a privileged structure, is present in molecules with a wide range of biological activities (see Figure ), − such as compounds 1 and 2 , which have shown excellent antiviral activity via inducing the plant’s defense response. , This framework has also been introduced to investigate antimicrobial activity for controlling plant diseases. For example, compound 3 , also named JHXJZ, is an antimicrobial agent in the registration stage of drug development .…”

Synthesis of new flavonoid derivatives based on 3-hydroxy-4′-dimethylamino flavone and study the activity of some of them as antifungal

“…We used a new method to prepare this compound according to the following [ 24 , 25 ]: (0.00177 mol, 0.5 g) of the flavonoid compound (A 2 ) were Dissolve in 50 ml of dry acetone, an excess of potassium carbonate K 2 CO 3 were added and stirred well for 5 min, then (0.00177 mol, 0.25 g) of methyl iodide dissolved in 10 ml acetone were added dropwise and stirred well for 48 h at 50–60 Cͦ. The reaction mixture were poured into a beaker containing crushed ice and neuterlised with dilute hydrochloric acid, the formed precipitate were filtered, washed with water and then recrystallized in absolute ethanol, resulting in a yellow precipitate.…”

Synthesis and biological evaluation of 4-phenoxy-phenyl isoxazoles as novel acetyl-CoA carboxylase inhibitors

“…MDA-MB-231 cells were plated on 6-well plates (3 × 10 4 cells/well) and incubated with various concentrations of 6g (0.75, 1.5, and 3 µM) and 6l (0.1, 0.2, and 0.4 µM) for 48 h. Then, cells were harvested by trypsinization and centrifugation, followed by staining with annexin-V-FITC in binding buffer for 15 min protected from light. Subsequently, the cells were stained with PI, and the proportion of apoptotic cells was measured by flow cytometer (Facs Canto II, Becton Dickinson, San Jose, CA, USA) 36 .…”