Novel 1,2,3-Triazole-Containing Quinoline-Benzimidazole Hybrids: Synthesis, Antiproliferative Activity, In Silico ADME Predictions, and Docking.

The newly synthesized quinoline-benzimidazole hybrids containing two types of triazole-methyl-phenoxy linkers were characterized via NMR and elemental analysis. Additional derivatization was achieved by introducing bromine at the C-2 position of the phenoxy core. These novel hybrids were tested for their effects on the growth of the non-tumor cell line MRC-5 (human fetal lung fibroblasts), leukemia and lymphoma cell lines: Hut78, THP-1 and HL-60, and carcinoma cell lines: HeLa and CaCo-2. The results obtained, presented as the concentration that achieves 50% inhibition of cell growth (IC50 value), show that the compounds tested affect tumor cell growth differently depending on the cell line and the dose applied (IC50 ranged from 0.2 to >100 µM). The quinoline-benzimidazole hybrids tested, including 7-chloro-4-(4-{[4-(5-methoxy-1H-1,3-benzo[d]imidazol-2-yl)phenoxy]methyl}-1H-1,2,3-triazol-1-yl)quinoline 9c, 2-(3-bromo-4-{[1-(7-chloroquinolin-4-yl)-1H-1,2,3-triazol-4-yl]methoxy}phenyl)-N-propyl-1H-benzo[d]imidazol-5-carboximidamide trihydrochloride 10e, 2-{4-[(1-{2-[(7-chloroquinolin-4-yl)amino]ethyl}-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-N-propyl-1H-benzo[d]imidazol-5-carboximidamide trihydrochloride 14e and 2-{3-bromo-4-[(1-{2-[(7-chloroquinolin-4-yl)amino]ethyl}-1H-1,2,3-triazol-4-yl)methoxy]phenyl}-N-propyl-1H-benzo[d]imidazol-5-carboximidamide trihydrochloride 15e, arrested the cell cycle of lymphoma (HuT78) cells. The calculated ADMET properties showed that the synthesized compounds violated at most two of Lipinski's rules, making them potential drug candidates, but mainly for parenteral use due to low gastrointestinal absorption. The quinoline-benzimidazole hybrid 14e, which was shown to be a potent and selective inhibitor of lymphoma cell line growth, obtained the highest binding energy (-140.44 kcal/mol), by docking to the TAO2 kinase domain (PDB: 2GCD).

Antioxidant and antiproliferative potentials of phenolic-rich extracts from biotransformed grape pomace in colorectal Cancer.

BACKGROUND: Colorectal carcinoma is one of the most commonly diagnosed malignancies worldwide. Consumption of dietary supplements and nutraceuticals such as phenolic compounds may help combat colorectal carcinoma. The effect of two phenolic-rich extracts prepared from biotransformed grape pomace on the antioxidant properties and antiproliferative activity against two colorectal cancer cell lines (Caco-2 and SW620) were investigated. METHODS: A 15-day solid-state fermentation with the white-rot fungi Phanerochaete chrysosporium and Trametes gibbosa was used to biotransform grape pomace. Solid-liquid extraction was then performed to extract bioactive compounds. The extract was analyzed for the determination of phenolic compounds by ultra-high performance liquid chromatography and in vitro assays of biological activities (antioxidant activity, antiproliferative activity, cell cycle analysis). RESULTS: The 4 days of solid-state fermentation proved to be the optimal period to obtain the maximum yield of phenolic compounds. The tested extracts showed significant antioxidant and antiproliferative activities. Grape pomace treated with P. chrysosporium and T. gibbosa reduced cancer cell growth by more than 60% at concentrations (solid/liquid ratio) of 1.75 mg/mL and of 2.5 mg/mL, respectively. The cell cycle perturbations induced by the grape pomace extracts resulted in a significant increase in the number of cells in the S (9.8%) and G2/M (6.8%) phases of SW620 exposed to T. gibbosa after 48 hours, while P. chrysosporium increased the percentage of cells in the G1 phase by 7.7%. The effect of grape pomace extracts on Caco-2 was less pronounced. CONCLUSIONS: The obtained results suggest the presence of bioactive compounds in biotransformed grape pomace as a residue from winemaking, which could be used to prevent colon cancer.

Effect of Wheatgrass Juice on Nutritional Quality of Apple, Carrot, Beet, Orange and Lemon Juice.

Fresh fruit and vegetable juices are commonly consumed as a valuable source of nutrients, while wheatgrass juice is, due to its nutritional value, used as a natural dietary supplement. The main aim of this research was to evaluate the effect of wheatgrass juice addition to apple, beet, carrot, orange, and lemon juice on total and in vitro bioaccessible concentrations of K, Ca, Mg, Mn, Fe, and Zn, vitamin C concentration, total phenolic and flavonoid content, and antioxidant activity. In comparison to other juices, wheatgrass juice had the highest total and in vitro bioaccessible concentrations of Ca, Mg, Mn, Fe, and Zn, while beet juice had the highest K concentration. Lemon and orange juices had the highest vitamin C concentration, while the highest total phenolic and flavonoid content were found in wheatgrass juice. After the addition of wheatgrass juice, Ca, Mg, Mn, and Zn concentration increased in all examined juices, vitamin C concentration increased in apple, beet, and carrot juice, total phenolic content increased in carrot juice, while total flavonoid content increased in apple, carrot, and orange juice. In comparison to the examined juices, wheatgrass juice has better nutritional value, and it could be used in a mixture with other juices to improve their nutritional value.

Autofermentation of Chamomile Ligulate Flowers Promote Antitumor Effects in vitro.

In the frame of this paper, the enzyme-assisted hydrolysis coupled with ultrasound and Soxhlet extraction was applied in order to get extracts of chamomile ligulate flowers (CLF). Obtained extracts were characterized in terms to their apigenin and apigenin glucoside composition, as well as antiproliferative potential against tumour cells. Antioxidant activity was determined by two different assays based on different mechanisms showing that autofermented extracts have higher reduction potential. Autofermented extracts prepared by ultrasound and Soxhlet extraction had a stronger impact on the treated carcinoma (HeLa and NCI-H358) and leukemia (K562) cells' growth reduction in comparison to the native extracts, 30-35% greater inhibition at the lowest concentration (0.01 mg/mL), in two observed time points (48 and 72 h). Leukemia cells are more sensitive to all tested extracts. The autofermented CLF extracts with highest antiproliferative efficacy induced morphological changes and apoptosis in the HeLa cells. Obtained results clearly showed that the combination of enzymatic hydrolysis with cavitation phenomenon results in extracts with higher apigenin content and increased biological potential.