Synthesis of thiazolidin-4-ones and thiazinan-4-ones from 1-(2-aminoethyl)pyrrolidine as acetylcholinesterase inhibitors

Figures & data

Figure 1. Similarity at chemical structure of acetylcholine, thiazolidin-4-ones (5) and thiazinan-4-ones (6).

Scheme 1. Synthetic pathway to the obtention of thiazolidinones and thiazinanones.

Figure 2. In vitro effect of compounds 5j, 6a, 6 h, 6j, 6k and 6n on the activity of AChE in cerebral cortex of rats. *p < .05, **p < .01, ***p < .001 when compared to control group (water or MeOH).

Figure 3. In vitro effect of compounds 5j, 6a, 6 h, 6j, 6k and 6n on the activity of AChE in cerebral hippocampus of rats. *p < .05, **p < .01, ***p < .001 when compared to control group (water or MeOH).

Figure 4. In vitro cytotoxicity activity of compounds 5j, 6a, 6 h, 6j, 6k and 6n to cell viability of the primary astrocyte culture at 100 μM, after for 48 h (A) and 72 h (B) the treatment.

Table 1. IC₅₀ of AChE inhibition for thiazolidin-4-ones 5 and thiazinan-4-ones 6.

	IC50 (µM)		R		IC50 (µM)
	Hippocampus	Cortex			Hippocampus	Cortex
5a	30.92	>250	H	6a	5.20	7.40
5g	>250	>250	4-Cl	6g	50.48	57.16
5h	105.40	>250	2-NO2	6h	92.80	11.03
5i	81.59	10.25	3-NO2	6i	29.42	50.55
5j	8.68	28.15	4-NO2	6j	9.32	40.06
5k	>250	>250	4-CH3	6k	4.46	6.83
5l	nd	nd	2-OCH3	6l	84.90	>250
5m	nd	nd	3-OCH3	6m	90.30	24.01
5n	>250	>250	4-OCH3	6n	17.02	22.20
5o	30.58	27.63	3-OH	6o	69.60	25.65

(nd) not determinated.