Figure 9
Drug candidates with basic amide moiety - protonated and alkylated. Panel (A) Cell viability (MTT assay) following exposure to modified variants of PP1 with basic amide moiety (25 μM, for 72 hrs). Panel (B) CV = Cell viability (% of control) mean ± SD at 25 μM; ClogP = calculated partitioning; HBD = hydrogen bond donor at pH = 7; HBA = hydrogen bond acceptor at pH = 7; logBB = calculated blood-brain partition; PSA = Polar surface area (Å2); MPA = Minimal projection area (Å2); LogS = Aqueous solubility (mg/ml); MPO = Central nervous system multiparameter optimization (CNS MPO). H32 CV at 10 μM (41.49 ± 7.94), CV at 5 μM (77.76 ± 7.24), and CV at 1 μM (96.80 ± 6.51). H35 CV at 10 μM (56.26 ± 0.59), CV at 5 μM (79.34 ± 1.70), and CV at 1 μM (93.64 ± 2.08). H37 CV at 10 μM (47.02 ± 1.23), CV at 5 μM (75.02 ± 1.42), and CV at 1 μM (109.20 ± 5.73). H38 CV at 10 μM (52.00 ± 1.86), CV at 5 μM (74.89 ± 1.79), and CV 1 μM (97.97 ± 11.41).
