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

Table 1 In vitro efficacy and selectivity measured by XTT of alkane aminoalcohol 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
1	H	H	H	9	97.8 ± 10.6	0.5	17.4 ± 0.4	0.2
2	H	H	H	13	348.4 ± 1.5	0.1	nt	–
3	H	H	H	15	239.3 ± 7.9	0.2	nt	–
4	H	H	Et	13	35.1 ± 0.1^c*	1.4	52.0 ± 5.3	1.5
5	H	H	Bu	9	297.6 ± 5.4	0.1	37.9 ± 1.9	0.1
6	H	H	Bu	13	31.9 ± 0.5^d*	1.5	52.0 ± 4.1	1.6
7	H	H	Bu	15	293.3 ± 2.6	0.1	10.0 ± 1.5	< 0.1
8	H	H	Hex	9	122.7 ± 6.4	0.4	43.2 ± 0.9	0.4
9	H	H	Hex	13	84.2 ± 4.3	0.5	10.9 ± 1.3	0.1
10	H	H	Hex	15	112.5 ± 5.3	0.4	54.2 ± 0.9	0.5
11	H	Et	Et	13	90.0 ± 5.7	0.5	2.2 ± 2.2	<0.1
12	H	Bu	Bu	9	169.0 ± 9.2	0.2	63.7 ± 1.2	0.4
13	H	Bu	Bu	13	192.1 ± 7.7	0.2	nt	–
14	Bn	H	H	13	67.6 ± 6.3	0.7	30.2 ± 0.3	0.4
15	Bn	H	Bu	13	232.0 ± 4.5	0.2	nt	–
Edelfosine					49.6 ± 0.5	1.0	40.7 ± 7.1	0.8

Abbreviations: Bn Benzyl, Bu Butyl, Et Ethyl, nt not tested, SEM standard error of the mean, R¹ substituent on the hydroxyl group; R² and R³ substituents on the amine group
^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 _{(15, 62)} = 413.82, P < 0.001; HDS P = 0.008)
^d*Significant increase in P_EDEL compared to edelfosine (ANOVA F _{(15, 62)} = 413.82, P < 0.001;^bHDS P = 0.002)

ISSN: 1756-3305