Synthesis and in vitro antiproliferative and antibacterial activity of new thiazolidine-2,4-dione derivatives

Figures & data

Figure 1. Synthesis of 2-(2,4-dioxothiazolidin-5-yl)acetyl chloride and 2-(2,4-dioxothiazolidin-5-ylidene)acetyl chloride. Reagent and conditions: (i) HCl, reflux; (ii) Br₂, CH₃COOH, reflux; (iii) SOCl₂, DMF, 1,4-dioxane, reflux 1 h.

Figure 2. Synthesis of target compounds (12–28) 2-(2,4-dioxothiazolidin-5-yl)acetic and 2-(2,4-dioxothiazolidin-5-ylidene)acetic acid derivatives. Reagent and conditions: (i) pyridine, 1,4-dioxane, rt, after 2 h acidified of solution of hydrochloric acid; (ii) 3-chlorobenzhydrazide or 2,4-dichlorobenzhydrazide, anhydrous ethanol, reflux; (iii) corresponding 4-substituted thiosemicarbazide derivatives, anhydrous ethanol, reflux.

Table 1. Antiproliferative activity of novel thiazolidine-2,4-dione derivatives and irinotecan used as a reference substance.

	A549		HepG2		MCF-7		BJ
Cell line compound	IC50 [µg/ml] ± SEM	SI [IC50BJ/IC50]	IC50 [µg/ml] ± SEM	SI [IC50BJ/IC50]	IC50 [µg/ml] ± SEM	SI [IC50BJ/IC50]	IC50[µg/ml] ± SEM
16					117.2 ± 1.23	1.39	163.3 ± 1.34
18	8.08 ± 1.05	1.24	3.86 ± 1.07	2.60	1.59 ± 1.06	6.32	10.05 ± 1.18
20			26.96 ± 1.02	0.42			11.35 ± 1.05
21			48.39 ± 1.02	0.65	124 ± 1.63	0.25	31.42 ± 1.08
22	57.27 ± 1.19	1.43	48.33 ± 1.07	1.69	72.02 ± 1.10	1.13	81.62 ± 1.11
23	31.31 ± 1.66	0.80	15.18 ± 1.25	1.66	34.18 ± 1.12	0.74	25.16 ± 1.52
Irinotecan – reference drug	39.69 ± 1.20	0.97	14.79 ± 1.24	2.62	21.08 ± 1.23	1.84	38.69 ± 1.37

Table 2. Newly synthesised compounds’ influence on the Gram-positive bacterial strains growth – MIC (μg/ml) values.

	Minimal inhibitory concentration MIC (μg/ml)
Compound	Staphylococcus aureus 25923	Staphylococcus aureus MIKROBANK 14.001	Staphylococcus epidermidis 12228
12	500	500	500
13	500	500	500
15	500	500	500
17	250	250	500
18	62.5	125	125
23	125	125	62.5
25	250	250	250
27	125	125	125
28	125	125	125