Herein lies the comprehensive archive of changelogs for every publicly released version of EMF. This may explain the higher anticancer activity of the most active hydrazide over its corresponding acid despite their nearly equipotent enzyme inhibition.The core mechanics module of Historical Immersion Project. Our study demonstrated that TBBt hydrazides are more lipophilic than their corresponding acids in contrast to the contradicting calculated lipophilicity using four well-known software programs. We are the first to experimentally estimate the lipophilicity of TBBt derivatives.
Molecular docking suggests that the hydrophilic group at N 2 of the TBBt triazole nucleus provides binding with important residues (Asp175, Lys68 and Trp176) in the ATP binding site of the CK2α enzyme. It induced apoptosis in the MCF-7 cell line through upregulation of bax (pro-apoptotic gene) four to five times higher than the corresponding ester or acid analogues. The most active compound incorporates an acetic acid hydrazide moiety at the N 2 of the TBBt triazole nucleus with IC 50 at 0.131 μM (CK2α), 9.1 μM (MCF-7) and 6.3 μM (A549). All the compounds demonstrated low sub-micromolar inhibition of CK2α and antiproliferative activity against both breast and lung cancer cell lines (MCF-7, and A549, respectively), at low micromolar concentrations with N 2-regioisomers exhibiting higher activity than their corresponding N 1-isomers. New compounds were prepared via N-alkylation of TBBt followed by base-catalysed hydrolysis or hydrazinolysis. A new series of antiproliferative casein kinase 2α (CK2α) inhibitors were synthesized incorporating either a hydrophilic group (carboxylic or hydrazide) or a hydrophobic group (ester) at N 1 or N 2 of 4,5,6,7-tetrabromobenzotriazole (TBBt).
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