Synthesis and biological evaluation of anti-Toxoplasma gondii activity of a novel scaffold of thiazolidinone derivatives

Figures & data

Scheme 1. General synthesis of the derivatives 1–33.

Figure 1. Invasion assay of ferrocene-based thiazolidinone derivatives (10 μM). VHL: vehicle (DMSO). *Significant inhibition of tachyzoite invasion (p ≤ .05, two-tailed Students’ t test). **Significant inhibition of tachyzoite attachment (p ≤ .05, two-tailed Students’ t test). Data are compiled from results of three independent experiments.

Figure 2. Replication assay of ferrocene-based thiazolidinone derivatives (10 μM). VHL: vehicle (DMSO); Tz: tachyzoites. Data are compiled from results of three independent experiments.

Table 1. Five-day growth inhibition assay for N-substituted thiazolidinone derivatives 1–33 and reference drugs.

Compound	Structure	IC50^a μM	IC90^b μM	TD50^c μM	TI^d
1		20	111	236	12
2		37	155	280	8
3		15	78	≥320	21
4		44	138	68	2
5		52	171	≥320	6
6		24	152	≥320	13
7		32	128	98	3
8		148	378	≥320	2
9		73	292	217	3
10		24	104	90	4
11		25	103	82	3
12		17	64	≥320	19
13		18	99	246	14
14		45	147	178	4
15		8	57	≥320	40
16		29	107	192	7
17		72	312	≥320	4
18		6	16	≥320	53
19		39	183	95	2
20		34	112	84	2
21		9	24	≥320	36
22		19	106	165	9
23		51	256	147	3
24		8	17	≥320	40
25		51	131	244	5
26		81	211	≥320	4
27		10	55	≥320	32
28		37	138	271	7
29		35	122	≥320	9
30		5	17	≥320	64
31		88	402	≥320	4
32		78	219	117	2
33		82	286	138	2
Sulfadiazine		43	219	281	7
Atovaquone		0.2	2	24	133

a IC₅₀= Median inhibitory concentration, a measure of tachyzoite inhibition.

b IC₉₀= Concentration at which 90% of the tachyzoite growth is inhibited.

c TD₅₀= Median toxicity dose, a measure of cytotoxicity against host cells.

d TI = Therapeutic index, a measure of efficacy, calculated by TD₅₀/IC₅₀. When TD₅₀ ≥320 TI = 320/IC₅₀.