Mirincamycin, an old candidate for malaria combination treatment and prophylaxis in the 21st century: in vitro interaction profiles with potential partner drugs in continuous culture and field isolates

Table 1 Results of mirincamycin in combination with DHA, CQ and TQ

	IC₅₀(nM)		IC₉₀(nM)		ΣFIC₅₀^a	ΣFIC₉₀^a
Tafenoquine – mirincamycin (n)	TQ	MIR	TQ	MIR
Field isolates (n^b = 3)	2,962.85	2,357.12	9,027.36	15,653.18	0.56	0.50
3D7 (n^c = 3)	1,348.48	19,539.36	2728.49	36,936.11	0.86	1.09
K1 (n^c = 2)	1,076.23	24,736.61	5,271.96	39,284.24	0.88	1.03
All tested isolates (n = 8)	1,829.64	8,135.69	5,005.97	25,786.65	0.78	0.83
DHA – mirincamycin (n)	DHA	MIR	DHA	MIR
Field isolates (n^b = 4)	3.23	1,067.34	13.0	20,101.72	0.81	0.69
3D7 (n^c = 3)	1.90	16,995.36	4.78	34,781.20	0.86	0.85
K1 (n^c = 2)	1.09	8,669.49	2.86	27,749.81	0.71	0.95
All tested isolates (n = 9)	2.12	4,276.94	6.65	25,925.12	0.80	0.83
Chloroquine – mirincamycin (n^b)	CHL	MIR	CHL	MIR
Field isolates (n^b = 2)	128.99	1,365.01	680.90	16,161.82	0.39	0.99
3D7 (n^c = 4)	28.27	23,288.21	63.87	38,311.62	1,06	1.04
K1 (n^c = 2)	651.93	18,869.50	1,174.69	36,535.66	0.95	0.99
All tested isolates (n = 8)	90.54	10,871.57	239.01	30,511.74	0.80	0.91

^aSynergy, <0.5; additivity, 0.5-2; antagonism,>2.
^bn, no. of fresh field isolates tested.
^cn, no. of repeats.
Geometric mean IC₅₀ and IC₉₀ in nM for mirincamycin (MIR), tafenoquine (TQ), chloroquine (CHL) and dihydroartemisinin (DHA) as well as the sum of fractional inhibitory (ΣFIC) concentrations for P. falciparum field isolates and culture clones 3D7 (chloroquine-sensitive) and K1 (chloroquine-resistant) tested in checkerboards assays.

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