The relationship of physico-chemical properties and structure to the differential antiplasmodial activity of the cinchona alkaloids

Table 1 Physicochemical parameters of Cinchona alkaloids. cpd. = compound, VAR = calculated vacuolar accumulation ratio. S = chloroquine-sensitive, R = chloroquine-resistant. S/R = ratio of IC50 values. BHIA = % inhibition in β-haematin inhibition test

Cpd.	pK_a1	pK_a2	Log P	Log D (pH7.4)	Log D (pH5.2)	VAR	IC50 nM S	IC50 nM R	RATIO S/R	BHIA % inhib.
Q	8.58a	4.12b	3.17c	1.97e	0.30	161.0	29.3¹⁵	103.2¹⁵	0.28	84 ± 1
			2.79d	1.96f	-0.25f
QD	8.58g	4.42h	2.84i	1.66j	0.40k	173.2	13.4¹⁵	43.7¹⁵	0.31	85 ± 9
			2.79d	1.63f	-0.61f
HQ	9.01 l	4.29	3.07	1.50	0.53	173.6	21.3¹⁵	151.7¹⁵	0.14	93 ± 0.6
			3.27d	1.45f	-0.79f
HQD	9.16	4.34	3.43	1.72	0.75	177.5	10.4¹⁵	74.1¹⁵	0.14	95 ± 0.4
			3.27d	1.66f	-0.59f
C	8.35m	4.28n	2.82o	1.85p	-0.38f	159.6	18.3⁴⁶	70.8⁴⁶	0.26	94 ± 0.5
			2.49d	1.82f
CD	8.40q	4.17r	2.68s	1.73t	-0.56f	157.5	69.5⁴⁶	206.8⁴⁶	0.34	94 ± 0.4
			2.49d	1.64f
EQ	9.54u	4.08	2.90	0.76	-1.44	169.2	3471¹⁵	1179¹⁵	2.94	2 ± 13
			2.79d	0.76f	-1.47f
EQD	9.39v	4.15	2.53	0.55	-1.2	170.8	2700¹⁵	1024¹⁵	2.64	12 ± 12
			2.79d	0.54f	-1.70f
CQ	10.18	8.38	4.72	0.96	-3.44	22750	18.5	264	0.07	81 ± 15
				0.92f	-3.44f
VE	8.4⁶²	<0	3.79⁶²	2.75f	0.59f	144.2	7200⁵³	2500⁵³	2.88	0 ± 21
PMZ	9.11⁴²	<0	4.75⁴²	3.03f	0.84f	155.5	1436⁵²	835⁵²	1.70	15 ± 22.5

a: Lit 8.43[64], 8.4[39], 8.05[65], 8.59[66]. In 80% methylcellosolve/20% water 7.73[41], 7.25[67] ; b: Lit. 4.34[64],4.32 [39], 4.33 [66]. In 80% methylcellosolve 2.81[67], 2.38[68] ; c: Lit. 3.44[22], 2.64[65] ; d: Calc. from CLogP ; e: Lit. 1.90[65], 2.14[22], 2.54[69], 1.73(pH7.0)[70] ; f: Calc from eqn. (1). ; g: Lit. 8.79[64], 7.95[41], 8.78[42]. In 80% methylcellosolve 7.95[41]7.36[67] ; h: Lit. 4.34[64], in 80% methylcellosolve 2.66[67], 2.40[68] ; i: Lit: 2.88[65], 3.71[42] ; j: Lit. 2.03[72], 2.07[74],2.11[31], 2.22[65]; k: Lit: -0.07[42] ; l: Lit. 8.87[40] ; m: Lit. 8.35[40], 8.32[65]. In 80% methylcellosolve 7.36[68] ; n: Lit. 4.28[67], In 80% methylcellosolve 2.80[67], 2.15[68] ; o: Lit 2.82[65]; p: Lit 1.85[65] ; q: Lit. 8.40[40], 8.30[65]; r: Lit. 4.17[40]. In 80% methylcellosolve 2.66[67], 2.12[68] ; s: Lit. 2.68[65] ; t: Lit. 1.73[65] ; u: Lit. In 80% methylcellosolve 8.44[41] ; v: Lit. in 80% methylcellosolve 8.32[41].

ISSN: 1475-2875