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. Author manuscript; available in PMC: 2020 May 9.
Published in final edited form as: J Med Chem. 2019 Apr 30;62(9):4669–4682. doi: 10.1021/acs.jmedchem.9b00274

Table 2.

TDP2 inhibitory activity, PAMPA permeability and cytotoxicity for analogues from phenolic OH modifications (11a-m).

graphic file with name nihms-1024966-t0006.jpg
Compd R TDP2 IC50 (μM)a PAMPA Pe (10−6 cm/s)b
4c -- 0.14 ± 0.01 0.008
11a H 0.20 ± 0.02 1.2
11b 4′ Cl 1.6 ± 0.2 0.4
11c 4′ Br 1.3 ± 0.0 0.2
11d 3′ Cl 0.99 ± 0.09 0.4
11e 3′ CO2Me 0.15 ± 0.01 0.6
11f 3′ CO2H 0.13 ± 0.01 0.01
11g H 1.1 ± 0.1 2.8
11h 4′ Cl >10 0.8
11i 4′ F 3.8 ± 0.3 2.7
11j 3′ CO2Me 0.93 ± 0.05 0.7
11k 3′ CO2H 0.19 ± 0.01 0.003
4b -- 0.041 ± 0.004 0.01
11l -- 0.38 ± 0.02 1.7
11m -- 0.30 ± 0.00 2.0
a

IC50: concentration of a compound producing 50% inhibition, expressed as mean ± standard deviation from three independent experiments performed in triplicate.

b

Pe: effective permeability coefficients determined using the PAMPA, measured in five replicates.