Synthesis, biological evaluation, and docking study of indole arylsulfonamides as aromatase inhibitors

In order to identify new aromatase enzyme inhibitors, thirty aryl sulfonamide derivatives containing anindole nucleus have been synthesized. The enzyme inhibition assay showed that four compounds inhibitaromatase in the sub-micromolar range. Loading concentrations of these four compounds were after-wards tested for cell viability and cytotoxicity on MCF7 human breast cancer cells, revealing a time- anddose-dependent decrease of active metabolizing cells over the time of the culture (0e72 h), starting froma concentration of 100mM. Likewise LDH released raised up to 40% at early time of exposures (24 h).Finally, the docking study showed that the best active compounds efficiently bound in the active site ofthe aromatase; high values of HBD and low levels of HBA are the principal requirement evidenced by theQSAR model.