Synthesis and antidiabetic activity of 2,4-thiazolidindione, imidazolidinedione and 2-thioxo-imidazolidine-4-one derivatives bearing 6-methyl chromonyl pharmacophore

Figures & data

Scheme 1.  General synthesis of IIIa–c, IVa–c, Va–c. (a) CH₃COONa/CH₃COOH, (b) Na₂CO₃/DMF.

Figure 1.  The molecular structure and atomic labeling scheme of compound Va.

Figure 2.  The molecular structure and atomic labeling scheme of compound Vb.

Figure 3.  The molecular structure and atomic labeling scheme of compound Vc.

Table 1.  Effects of various compounds on glucose-mediated insulin release from INS-1 cells.*

Compounds	Concentration (mg/mL)	Insulin release (% of glucose effect at 5.6 mM)
Glucose [3.0 mM] (sub-stimulatory concentration, control)		80.02 ± 2.82*
Glucose [5.6 mM]		100.0
Plus IIIa^Citation15	0.001	90.53 ± 8.10
	0.01	75.61 ± 13.92
Plus IIIb	0.001	115.9 ± 12.69 (n = 5)
	0.01	114.7 ± 9.66** (n = 5)
Plus IIIc	0.001	113.1 ± 12.07 (n = 3)
	0.01	116.3 ± 14.26 (n = 3)
Plus IVa	0.001	120.6 ± 13.53* (n = 7)
	0.01	152.0 ± 9.79** (n = 4)
Plus IVb	0.001	113.3 ± 10.57* (n = 4)
	0.01	129.9 ± 13.75** (n = 4)
Plus IVc	0.001	107.0 ± 19.04 (n = 6)
	0.01	113.3 ± 9.70** (n = 6)
Plus Va	0.001	116.2 ± 16.58** (n = 5)
	0.01	106.4 ± 4.83 (n = 5)
Plus Vb	0.001	98.87 ± 6.92 (n = 4)
	0.01	122.4 ± 9.90 (n = 4)
Plus Vc	0.001	116.0 ± 15.61 (n = 3)
	0.01	141.9 ± 13.41** (n = 3)
Plus glibenclamide  (positive control)	0.001	145.7 ± 7.74**(n = 22)
Plus DMSO	0.001	102.8 ± 4.94 (n = 13)
	0.01	101.7 ± 7.03 (n = 14)

*INS-1 cells in multi-wells were washed three times and incubated in KRBH-buffer for 90 min at 5.6 mM glucose. The results are expressed as percent insulin release at 5.6 mM glucose alone. Values obtained in the presence of 3.0 mM glucose (substimulatory concentration) and glibenclamide (1 µg/mL) served as negative and positive controls. The final concentration of the solvent DMSO was either 0.01 or 0.1 %; a DMSO control (even at 1 %) had no major effect as shown in the Table data. Each value represents the mean ± S.E.M. *p < 0.05; **p < 0.01 vs. effect of 5.6 mM glucose alone.

Verspohl EJ, Bozdağ-Dündar O, Kaup RM, Bauer K, Ertan R. Insulinotropic activity of chromonyl-2,4-thiazolidinediones. Med Chem Res 2009;18: 665–670.

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