Table 2.

Activities of phenylpyrimidine congeners against somule and adult S. mansoni, their ability to stabilize acetylated tubulin, and mobility measurements by WormAssay.

	Structure				Somules (1 μM)a		Somules (10 μM)a		Adults (5 μM)a			Fold-change in acetylated α- tubulinb	WormAssay (average adult worm movement ± SD)c (5 μM)
Cpd#	R1	R2	R3	het	24 h	48 h	24 h	48 h	5 h	24 h	48 h	4 h	5 h
21			Cl		N	N	R, deg	R, deg	N	N	S, on sides	1.95 ± 0.2 (1 μM)	75.3 ± 18.9
22			Cl		R, deg	R, deg	R, deg	R, deg	N	N	Unc	2.68 ± 0.04 (1 μM)	131.4 ± 27.4
23			Cl		Deg, unc	Deg, unc	Deg, unc	Deg, unc	Unc, darkd	Unc, darkd	Unc, darkd	4.1 ± 0.3 (1 μM)	62.1 ± 26.4d
24			Cl		N	N	N	Deg, unc	Sd	Unc, on sidesd	S, dark, on sidesd	2.7 ± 0.2 (10 μM)	56.0 ± 21.5d
25			Cl		R, S	R, S	R, I	R, I,	I, on sides	I, on sides	I, on sides	3.0 ± 0.6 (10 μM)	5.5 ± 9.8
26			H		R, S	R	R, S	R, S	Sd	Unc, on sidesd	S, dark, on sidesd	NSe	11.0 ± 14.7d
27			Cl		R, S	R	R, I	R, I	I, on sides	I, on sides	I, on sides	NS	6.3 ± 9.3
28			Cl		R, I	R, I	R, I	R, I	I, on sides	I, on sides	I, on sides	NS	2.9 ± 8.8
29			Cl		R, S	R, S	R, I	R, I	I, on sides	I, on sides	I, on sides	NS	5.0 ± 11.5
30			Cl		S	S, R	R, I	R, I	S, on sides	S, on sides	S, on sides	2.25 ± 0.51 (10 μM)	12.9 ± 18.1
31	H		Cl		R, unc	N	R, unc	N	N	N	N	NS	89.0 ± 18.6
32		H	Cl		N	N	R, S	N	N	N	N	NS	78.0 ± 20.1
PZQ					Unc	Unc	Deg	Deg	Deg	D	D	NTf	1.8 ± 5.1
DMSO					N	N	N	N	N	N	N		104.1 ± 24.4

^aDescriptors are listed in the footnote to Table 1 and their corresponding severity scores are provided in Scheme 1. Data are from a minimum of two experiments each in duplicate and representative data are shown.

^bELISA measured the relative changes in acetylated α-tubulin levels after incubation of HEK293 cells with compound for 4 h. Compounds were assessed in triplicate wells within a single experiment.

^cWormAssay employed a movie camera connected to a Mac computer and an open source software to record the average motion of adult worms in each well.^{38, 39}

^dAssays performed at 10 μM.

^eNS = Non-significant; changes in AcTub levels observed after 4 h of incubation with either 1 or 10 μM of test compound did not reach statistical significance as determined by one-way ANOVA.

^fNT = not tested