Combined modifications produced mixed results with mid-nanomolar range AC1 potencies but slightly improved AC8 selectivity. Several analogs are within a range for AC1 activity and AC8 potency that would make them reasonable to advance toward in vivo efficacy assays, thus, we prioritized analogs 16, 20, 38 and 39 for further evaluation (dose-response curves provided in toxicity in the HEK cells utilized for the assay. However, to ensure that the molecules did not have undesired cytotoxicity we assessed compounds 16, 20, 38, and 39 in the CellTiter-Glo assay when incubated with HEK293 cells at 30 µM for 1 hour. Across the group of five analogs there was no reduction in cell viability indicating the scaffold is non-toxic to this human cell line (Table ).