Antiplasmodial dihetarylthioethers target the coenzyme A synthesis pathway in Plasmodium falciparum erythrocytic stages

Table 2 Physicochemical properties of selected test compounds in comparison to Amb180780

ID	M_r	TPSA	Calc. log P	S_{0, exp} [µM]^a	Log S_{0, exp}	Log S_calc.
3a	302.33	131.38	3.49	<1.0^b	<−6.00	−5.30
8c	248.33	97.14	2.58	1.78 × 10^{3 d}	−2.75	−4.06
8d	251.35	120.45	3.30	36.4^c	−4.44	−4.78
8e (Kuwei173)	235.29	105.35	2.83	1.33 × 10^{3 c}	−2.88	−3.82
8f	267.35	159.36	2.28	4.4^c	−5.36	−5.38
8g	284.36	108.00	3.72	0.43^d	−6.37	−5.82
8k	285.35	120.89	3.11	77.0^c	−4.11	−5.33
Amb180780	265.38	120.45	3.61	nd	nd	−5.94

The prediction of physicochemical parameters was performed through Swiss ADME. Calculation of TPSA according to Ertl et al. [13]; lipophilicity prediction according to Wildman et al. [14], solubility prediction according to Ali et al. [15]; Lipinski violations according to Lipinski [16]
nd not determined
^aDetermination of thermodynamic solubility in aqueous buffer (pH 7.4) with shake flask method using HPLC
^bMINIMAL detectable concentration of 3a by HPLC/UV
^cEquilibrium after 24 h
^dEquilibrium after 48 h

ISSN: 1475-2875