Design, synthesis, characterization and cytotoxic activity of new ortho-hydroxy and indole-chalcone derivatives against breast cancer cells (MCF-7)

Twenty-seven new ortho-hydroxy chalcone and a series of indole-chalcone derivatives have been designed and synthesized. The structures of all newly-synthesized compounds were characterized by different spectroscopic techniques and the interactions with tubulin were evaluated for antiproliferative activities in vitro. The structure-activity relationships were elucidated for compounds with various substituents on the benzene ring of the aldehyde moiety at positions C-3, C-4 and C-5 with constant o-OH. The best inhibition results of ring bioisoterism for cancer cell growth were obtained for compounds 4c, 5j, and 6a with substituents m-tBu, Br and p-OCH3, respectively. Their antiproliferative activity was evaluated in MCF-7 cells, with compound 5j showing cytotoxicity activity comparable to that of reference compound paclitaxel. A computational study was carried out, for calculation of pharmacophore pattern, prediction of pharmacokinetic properties and toxicity. The results of the target compounds are followed by docking studies that have provided structural recommendations for designing new antiproliferative chalcones. [GRAPHICS] .

Automated summary

Twenty-seven new ortho-hydroxy chalcone and a series of indole-chalcone derivatives were designed and synthesized. Their structures were characterized by spectroscopic techniques and their interactions with tubulin were evaluated for antiproliferative activities. The study found that the position and nature of substituents on the compounds have an effect on their inhibition results. Compounds 4c, 5j, and 6a showed the best inhibition of cancer cell growth.