Höfundar:
Elvar Örn Viktorsson
Introduction:
The natural products iodinin and myxin are well known antibiotics from the phenazine class of natural products. Myxin is particularly known for potent and broad-spectrum antimicrobial effects. Iodinin, a close natural derivative of myxin was recently discovered to be a selective apoptotic inducer of leukemic cell death. The presented work will cover synthesis and biological evaluations of new phenazine 5,10-dioxides aimed towards the targeting of acute myeloid leukemia (AML).
Methodology:
Iodinin and myxin were synthesized from commercially available reagents and various prodrugs and structural analogs constructed. Structure-activity relationship (SAR) studies were conducted by assessing cytotoxicity of multiple iodinin/myxin analogs against both leukemic and non-malignant cell lines. A cell proliferation reagent (WST-1) was used to assess the viability.
Results:
More than one hundred analogs of iodinin and myxin have been synthesized and biologically assessed. Carbamate analogs of phenazine 5,10-dioxides proved to be the most attractive in terms of high potency and selectivity towards the AML cells. Preliminary results indicate that a regioisomer of iodinin should be pursued further in terms of drug development.
Conclusions:
The presentation summarizes our recent efforts in developing new phenazine 5,10-dioxides to target acute myeloid leukemia.