In vitro and in vivo evaluation of 2-aminoalkanol and 1,2-alkanediamine derivatives against Strongyloides venezuelensis

Table 2 In vitro efficacy and selectivity measured by XTT of alkane diamines derivatives against S. venezuelensis third-stage larvae (L3)

Compound	R¹	R²	R³	n	Efficacy against L3	P_EDEL ^a	Cytotoxicity	SI^b
					LC₅₀ (μM)		LC₅₀ (μM)
					Mean ± SEM		Mean ± SEM
16	H	H	H	13	75.0 ± 4.1	0.6	40.1 ± 0.4	0.5
17	H	H	Boc	9	39.0 ± 2.9^c*	1.2	66.6 ± 2.2	1.7
18	H	H	Boc	13	39.1 ± 4.7^c*	1.2	56.2 ± 3.3	1.4
19	H	H	Boc	15	45.7 ± 9.2	1.0	36.8 ± 2.8	0.8
20	H	Et	H	13	95.4 ± 1.5	0.5	10.5 ± 1.4	0.1
21	H	Bu	H	13	148.3 ± 3.3	0.3	15.5 ± 1.2	0.1
22	H	Hex	H	13	83.6 ± 3.1	0.5	5.2 ± 0.5	0.0
23	H	Hex	Boc	13	38.9 ± 4.6^c*	1.2	4.9 ± 0.8	0.1
24	Et	Et	H	13	33.4 ± 0.7 ^d*	1.4	13.2 ± 1.7	0.3
25	Hex	Hex	Boc	13	67.8 ± 7.1	0.7	7.6 ± 0.6	0.1
Edelfosine					49.6 ± 0.5	1.0	40.7 ± 7.1	0.8

Abbreviations: Bn Benzyl, Bu butyl, Et ethyl, Hex hexyl, Boc, tert-butoxycarbonyl, SEM standard error of the mean; R1 and R2 substituents on the amine at position C-1; R3 substituents on the amine at position C-2
^aPotency relative to edelfosine (P_EDL) = Compound-LC₅₀ against L3 / Edelfosine-LC₅₀ against L3
^bSelectivity index (SI) = Compound-LC₅₀ to macrophages/Compound-LC₅₀ against L3
^c*Significant increase in P_EDEL compared to edelfosine ANOVA: F _{(10, 72)} = 216.85, P < 0.001; HDS P = 0.001
^c*Significant increase in P_EDEL compared to edelfosine ANOVA: F _{(10, 72)} = 216.85, P < 0.001; HDS P < 0.001

ISSN: 1756-3305