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Synthesis, Computational Study, and In Vitro α-Glucosidase Inhibitory Action of Thiourea Derivatives Based on 3-Aminopyridin-2(1<i>H</i>)-Ones
oleh: Zarina Shulgau, Irina Palamarchuk, Shynggys Sergazy, Assel Urazbayeva, Alexander Gulyayev, Yerlan Ramankulov, Ivan Kulakov
Format: | Article |
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Diterbitkan: | MDPI AG 2024-07-01 |
Deskripsi
Reactions with allyl-, acetyl-, and phenylisothiocyanate have been studied on the basis of 3-amino-4,6-dimethylpyridine-2(1<i>H</i>)-one, 3-amino-4-phenylpyridine-2-one, and 3-amino-4-(thiophene-2-yl)pyridine-2(1<i>H</i>)-one (benzoyl-)isothiocyanates, and the corresponding thioureide derivatives <b>8-11a-c</b> were obtained. Twelve thiourea derivatives were obtained and studied for their anti-diabetic activity against the enzyme α-glucosidase in comparison with the standard drug acarbose. The comparison drug acarbose inhibits the activity of α-glucosidase at a concentration of 15 mM by 46.1% (IC<sub>50</sub> for acarbose is 11.96 mM). According to the results of the conducted studies, it was shown that alkyl and phenyl thiourea derivatives <b>8,9a-c</b>, in contrast to their acetyl–(benzoyl) derivatives and <b>10,11a-c</b>, show high antidiabetic activity. Thus, 1-(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)-3-phenylthiourea <b>9a</b> has the highest inhibitory activity against the enzyme α-glucosidase, exceeding the activity of the comparison drug acarbose, which inhibits the activity of α-glucosidase by 56.6% at a concentration of 15 mm (IC<sub>50</sub> = 9,77 mM). 1-(6-methyl-2-oxo 4-(thiophen-2-yl)-1,2-dihydropyridin-3-yl)-3-phenylthiourea <b>9c</b> has inhibitory activity against the enzyme α-glucosidase, comparable to the comparison drug acarbose, inhibiting the activity of α-glucosidase at a concentration of 15 mm per 41.2% (IC<sub>50</sub> = 12,94 mM). Compounds <b>8a, 8b,</b> and <b>9b</b> showed inhibitory activity against the enzyme α-glucosidase, with a lower activity compared to acarbose, inhibiting the activity of α-glucosidase at a concentration of 15 mM by 23.3%, 26.9%, and 35.2%, respectively. The IC<sub>50</sub> against α-glucosidase for compounds <b>8a</b>, <b>8b</b>, and <b>9b</b> was found to be 16.64 mM, 19.79 mM, and 21.79 mM, respectively. The other compounds <b>8c, 10a, 10b, 10c, 11a, 11b</b>, and <b>11c</b> did not show inhibitory activity against α-glucosidase. Thus, the newly synthesized derivatives of thiourea based on 3-aminopyridine-2(1<i>H</i>)-ones are promising candidates for the further modification and study of their potential anti-diabetic activity. These positive bioanalytical results will stimulate further in-depth studies, including in vivo models.