New prodrugs and analogs of the phenazine 5,10-dioxide natural products iodinin and myxin promote selective cytotoxicity towards human acute myeloid leukemia cells
Elvar Örn Viktorsson, Reidun Aesöy, Sindre Støa, Viola Lekve, Stein Ove Døskeland, Lars Herfindal, Pål Rongved
Abstract
) displayed increased cytotoxic potency in MOLM-13 cells compared to all the other compounds studied. On the other hand, dihalogenated compounds displayed high toxicity towards the cardiomyoblast H9c2 cell line, while MOLM-13 selectivity of the 7,8-dimethylated analogs were less affected. Further, a parallel artificial membrane permeability assay (PAMPA) demonstrated the majority of the synthesized compounds to penetrate cell membranes efficiently, which corresponded to their cytotoxic potency. This work enhances the understanding of the structural characteristics essential for the activity of phenazine 5,10-dioxides, rendering them promising chemotherapeutic agents.