O’Boyle, Niamh M. published the artcileSynthesis and evaluation of antiproliferative microtubule-destabilising combretastatin A-4 piperazine conjugates, Quality Control of 104-01-8, the main research area is piperazine conjugate preparation antitumor microtubule human SAR docking cytotoxicity.
Design, synthesis, biochem. evaluation and mol. modeling studies were described for the series of analogs of the microtubule-destabilizing agent, combretastatin A-4 (CA-4) I [R1 = H, OH, OMe, NO2, F; R2 = OH, OMe; R3 = OH, piperazin-1-yl, 1,4-diazepan-1-yl, etc.] and II [R4 = H, OH; R5 = OH, piperazin-1-yl, 4-phenylpiperazin-1-yl, etc.] contain the CA-4 core structure with modifications to the stilbene linking group, and were predominantly piperazine derivatives Synthesis was achieved in a two-step process by firstly obtaining the acrylic acid via a Perkin reaction using microwave enhanced synthesis, followed by coupling using either DCC or Mukaiyama’s reagent. All target compounds I and II were screened for antiproliferative activity in MCF-7 breast cancer cells, among them compounds, I [R1 = OH; R2 = OMe, R3 = 4-phenylpiperazin-1-yl] displayed potent antiproliferative activity (IC50 = 190 nM). Two amino-containing derivatives, I [R1 = NH2; R2 = OMe; R3 = 4-benzylpiperazin-1-yl, 4-(p-tolyl)piperazin-1-yl] were the most potent with IC50 values of 130 nM and 83 nM resp. Representative compounds were shown to depolymerize tubulin, induce G2/M arrest and apoptosis in MCF-7 cells but not peripheral blood mononuclear cells and induce cleavage of the DNA repair enzyme poly ADP ribose polymerase (PARP) in MCF-7 cells. Modeling studies predicted that the compounds I and II bind to tubulin within the colchicine-binding site.
Organic & Biomolecular Chemistry published new progress about Antitumor agents. 104-01-8 belongs to class isoquinoline, name is 4-Methoxyphenylacetic acid, and the molecular formula is C9H10O3, Quality Control of 104-01-8.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem