Cytotoxic 1,2,3-Triazoles as Potential Leads Targeting the S100A2-p53 Complex: Synthesis and Cytotoxicity.

In silico screening predicted 1 (N-(4-((4-(3-(4-(3-methoxyphenyl)-1H-1,2,3-triazol-1-yl)propyl)piperazin-1-yl) sulfonyl)-phenyl)acetamide) as an inhibitor of the S100A2-p53 protein-protein interaction. S100A2 is a validated pancreatic cancer drug target. In the MiaPaCa-2 pancreatic cell line, 1 was a ∼50 µM growth inhibitor. Synthesis of five focused compound libraries and cytotoxicity screening revealed increased activity from the presence of electron withdrawing moieties on the sulfonamide aromatic ring, with the 3,5-bis-CF3 Library 3 analogues the most active, with GI50 values of 0.91 (3-ClPh; 13 i; BxPC-3, Pancreas) to 9.0 µM (4-CH3 ; 13 d; PANC-1, Pancreas). Activity was retained against an expanded pancreatic cancer cell line panel (MiaPaCa-2, BxPC-3, AsPC-1, Capan-2, PANC-1 and HPAC) and the normal cell line MCF10A (breast). Bulky 4-disposed substituents on the terminal phenyl ring enhanced broad spectrum activity with growth inhibition values spanning 1.1 to 3.1 µM (4-C(CH3 )3 ; 13 e; BxPC-3 and AsPC-1 (pancreas), respectively). Central alkyl spacer contraction from propyl to ethyl proved detrimental to activity with Library 4 and 5.5- to 10-fold less cytotoxic than the propyl linked Library 2 and Library 3. The data herein was consistent with the predicted binding poses of the compounds evaluated. The highest levels of cytotoxicity were observed with those analogues best capable of adopting a near identical pose to the p53-peptide in the S100A2-p53 binding groove.

Fruit characteristics, phytochemical and antioxidant properties of blueberry ash (Elaeocarpus reticulatus).

Blueberry ash (Elaeocarpus reticulatus Sm.) fruit has potential for human nutrition, but there is limited information on this fruit. This preliminary study aimed to characterise blueberry ash fruit and examine the influence of extraction solvents on its phytochemical and antioxidant properties. Blueberry ash fruit is dark blue in colour and is a stone fruit of small size (7 mm) and light weight (0.2 g). However, it has a high portion of flesh (60% of fruit weight), which is edible and can be a potential source of phytochemicals. Water, ethanol, acetonitrile, acetone, and their combination were tested for extraction of phytochemicals from flesh of this fruit. Water or absolute organic solvent was ineffective for extraction of phenolic compounds from this fruit, but mixtures of water and organic solvents were more effective, and 50% acetone was the most suitable extraction solvent. Extraction with 50% acetone, this fruit was found to contain high levels of total phenolic content, flavonoids, proanthocyanidins, and anthocyanins (104 mg GAE/g, 155 mg RUE/g, 78 mg CE/g, and 119 mg CGE/g, respectively). In addition, this fruit was found to possess potent antioxidant properties. Therefore, this fruit should be further studied for identification of its phenolic compounds and further tested for their biological properties.