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Table 2 Comparison of biological, structural and physicochemical properties of improved congener 4h and prototype 1

From: Structure–activity relationships in a series of antiplasmodial thieno[2,3-b]pyridines

ID IC50 [µM], PfGSK-3a (Kinase Glo Plus) IC50 [µM], HsGSK-3a (Kinase Glo Plus) IC50 [µM], PfGSK-3b (radiometric) IC50 [µM], PfNF54-Luc IC50 [µM], HEK
293Tc
SId TPSA [Å2]e Fsp3 f S0 p H 7.4, exp [µM]g
1 0.24 (0.21–0.27) 9.08 (6.72–12.5) 0.151 (0.154–0.148) 5.5 35.2 (27.0–46.3) 6.4 134.0 0.00 1.5 ± 0.3
4h 0.72 (0.68–0.75) 40.2 (38.3–42.2) 0.184 (0.179–0.190) 1.2 5.56 (5.05–6.03) 4.6 140.5 0.19 4.8 ± 0.9
  1. aKinase Glo Plus assay, mean value of three determinations, range given in brackets
  2. bRadiometric assay, mean value of two determinations, range given in brackets
  3. cHEK293T cell viability assay, mean value of six determinations, range given in brackets
  4. dSI (selectivity index) = IC50 HEK293T/IC50 PfNF54-Luc
  5. eCalculation of TPSA according to Ertl et al. [33] through Swiss ADME [32]
  6. fNumber of sp3 hybridized carbons/total carbon count [26]
  7. gKinetic solubility determined by nephelometry in aqueous buffer (pH 7.4) in the presence of 1% DMSO [42, 43]; mean ± standard deviation