Synthesis and characterisation of thiobarbituric acid enamine derivatives, and evaluation of their α-glucosidase inhibitory and anti-glycation activity

Figures & data

Scheme 1. Synthetic route for the synthesis of 3a–k, 4a–d, 5, and 6.

Table 1. Result of in vitro α-glucosidase enzyme inhibitor and anti-glycation activities.

Compound	Structure	Anti-glycation assay IC50 ± SEM (µM)	α-Glucosidase IC50 ± SEM (µM)
3a		88.57 ± 0.37^b	NA
3b		80.36 ± 0.74^b	NA
3c		82.22 ± 4.36^b	NA
3d		130.53 ± 3.15^b	NA
3e		77.28 ± 0.72^b	NA
3f		81.74 ± 1.39^b	NA
3g		82.36 ± 5.09^b	397.45 ± 0.98^a
3h		70.92 ± 1.84^b	NA
3i		75.13 ± 0.65^b	264.07 ± 1.87^a
3j		101.92 ± 1.7^b	433.33 ± 2.34^a
3k		ND	ND
4a		NA	NA
4b		NA	NA
4c		NA	NA
4d		NA	NA
5		554.76 ± 9.1^b	448.63 ± 2.46^a
6		31.5 ± 0.81^a	NA
Rutin		54.59 ± 2.20	–
Acarbose		–	875.75 ± 2.08

^a Significant activity.

^b Moderate activity.

ND: not determined; NA: not active.

Figure 1. Lead compounds 3i and 6 with promising activities.

Figure 2. Binding mode of thiobarbituric acid derivatives into the α-glucosidase binding cavity. For clarity, acarbose is shown in cyan. Compounds 3g, 3i, and 3j are indicated in pink, and 5 in green. The part of the enzyme in the background is shown as surface model.

Figure 3. Interactions of acarbose with crucial residues of α-glucosidase.

Figure 4. The predicted binding interactions of compounds 3g, 3i, 3j, and 5 in the active site.