In this research, antioxidant activities of various extracts obtained from Humulus lupulus L. were compared by DPPH, ABTS, FRAP, and CUPRAC assays. The amount of total phenolic components determined by the Folin-Ciocalteu reagent was found to be highest for 25% aqueous ethanol (9079 ± 187.83 mg Ferulic acid equivalent/100 g extract) and methanol-1 (directly) (8343 ± 158.39 mg Ferulic acid equivalent/100 g extract) extracts. The n-hexane extract of H. lupulus exhibited the greatest with DPPH (14.95 ± 0.03 μg Trolox equivalent/g sample). The highest phenolic content in the ethanolic extract could be the major contributor to its highest CUPRAC activity (3.15 ± 0.44 mmol Trolox equivalent/g sample). Methanol-2 (n-hexane, acetone, and methanol) and methanol-3 (n-hexane, dichloromethane, ethylacetate, and methanol) extracts, respectively, exhibited the most potent ABTS (7.35 ± 0.03 mM Trolox equivalent) and FRAP (1.56 ± 0.35 mmol Fe(2+)/g sample) activities. Some of the components from the crude extracts were determined by LC-MS/MS and GC-MS analyses. Comparative screening of antioxidant activities of H. lupulus extracts and quantification of some major components by LC-MS/MS, qualitatively analysis of the reported ones which were optimal under negative ion SIM mode and coinjection, are going to be valuable for food and health applications.
Eukaryotic
elongation factor-2 kinase (eEF-2K) is an unusual alpha
kinase commonly upregulated in various human cancers, including breast,
pancreatic, lung, and brain tumors. We have demonstrated that eEF-2K
is relevant to poor prognosis and shorter patient survival in breast
and lung cancers and validated it as a molecular target using genetic
methods in related in vivo tumor models. Although
several eEF-2K inhibitors have been published, none of them have shown
to be potent and specific enough for translation into clinical trials.
Therefore, development of highly effective novel inhibitors targeting
eEF-2K is needed for clinical applications. However, currently, the
crystal structure of eEF-2K is not known, limiting the efforts for
designing novel inhibitor compounds. Therefore, using homology modeling
of eEF-2K, we designed and synthesized novel coumarin-3-carboxamides
including compounds A1, A2, and B1–B4 and evaluated their activity by performing in silico analysis and in vitro biological assays in breast
cancer cells. The Molecular Mechanics/Generalized Born Surface Area
(MM/GBSA) area results showed that A1 and A2 have interaction energies with eEF-2K better than those of B1–B4 compounds. Our in vitro results indicated that compounds A1 and A2 were highly effective in inhibiting eEF-2K at 1.0 and 2.5 μM
concentrations compared to compounds B1–B4, supporting
the in silico findings. In conclusion, the results
of this study suggest that our homology modeling along with in silico analysis may be effectively used to design inhibitors
for eEF-2K. Our newly synthesized compounds A1 and A2 may be used as novel eEF-2K inhibitors with potential therapeutic
applications.
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