TABLE 4.

Toxicities and antileishmanial activities of 7-substituted 9-chloro and 9-aminoacridines of the A series

Compound	R1	R2	Physicochemical propertiesa			Pab	Toxicity (IC50, μM)	Antileishmanial activity (IC50, μM)c
			Log P	Log S	pKa			PRO	AMA	SI
A2	NH2	CH3	3.20	−3.94	7.17	0.748	73.4	0.5	0.4	183.5
A3	NH2	CH3OH	2.05	−3.90	14.14	0.764	56.6	5.4	4.1	13.8
A4	NH2	CH3Br	3.66	−5.19	6.60	0.650	86.2	3.6	4.6	18.7
A48	NH2	C4H8O3	2.88	−4.63	6.83	0.667	54.4	2.4	1.3	41.8
A66	NH2	C6H12O2	3.67	−5.00	6.83	0.660	53.9	3.1	2.5	21.5
A65	NH2	C7H14O2	3.99	−5.22	6.83	0.631	5.4	2.2	Toxic
A57	NH2	C9H10O2	4.33	5.77	6.65	0.658	6.9	0.4	0.2	34.5
A64	NH2	C9H9FO2	4.50	−6.36	6.65	0.536	19.9	1.3	0.6	33.2
A55	NH2	C9H9ClO2	4.91	−6.48	6.65	0.702	152.2	76.1	45.6	3.3
A62	NH2	C10H12O3	4.23	−6.04	6.67	0.669	3.2	1.9	Toxic
A8	Cl	CH3	4.35	−5.04		0.686	171.6	1.1	2.3	74.6
A43	Cl	CH3OH	3.27	−4.81	13.99	0.713	91.3	182.6	9.1	10.1
A6	Cl	CH3Br	4.99	−6.18		0.596	95.1	50.5	14.8	6.4
A50	Cl	C4H8O3	4.19	−5.61		0.616	226.1	150.7	75.3	3.0
A53	Cl	C6H12O2	4.90	−5.95		0.613	109.2	50.9	42.5	2.5
A61	Cl	C7H14O2	5.07	−6.19		0.587	209.6	27.9	36.4	5.7
A52	Cl	C9H10O2	5.31	−6.96		0.605	132.3	136.5	Toxic
A44	Cl	C9H9FO2	5.00	−7.28		0.482	189.4	197.1	44.2	4.3
A46	Cl	C9H9ClO2	5.42	−5.38		0.644	155.3	156.3	155.4
A54	Cl	C10H12O3	5.31	−6.97		0.615	122.5	125.4	122.6

^aLog P lipophilicity; log S, solubility in water.

^bP_a, predicted value for antileishmanial activity.

^cPRO, activity towards Leishmania promastigotes; AMA, activity towards Leishmania amastigotes; SI, ratio between antileishmanial activity on amastigotes and toxicity.