The Synthesis, In Vitro Bio-Evaluation, and In Silico Molecular Docking Studies of Pyrazoline-Thiazole Hybrid Analogues as Promising Anti-α-Glucosidase and Anti-Urease Agents
In the present work, a concise library of benzothiazole-derived pyrazoline-based thiazole (<b>1</b>-<b>17</b>) was designed and synthesized by employing a multistep reaction strategy. The newly synthesized compounds were screened for their α-glucosidase and urease inhibitory...
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| Main Authors: | , , , , , , , , |
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| Format: | Book |
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MDPI AG,
2023-11-01T00:00:00Z.
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| Summary: | In the present work, a concise library of benzothiazole-derived pyrazoline-based thiazole (<b>1</b>-<b>17</b>) was designed and synthesized by employing a multistep reaction strategy. The newly synthesized compounds were screened for their α-glucosidase and urease inhibitory activities. The scaffolds (<b>1</b>-<b>17</b>) were characterized using a combination of several spectroscopic techniques, including FT-IR, <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, and EI-MS. The majority of the synthesized compounds demonstrated a notable potency against <i>α</i>-glucosidase and urease enzymes. These analogues disclosed varying degrees of <i>α</i>-glucosidase and urease inhibitory activities, with their IC<sub>50</sub> values ranging from 2.50 to 17.50 μM (<i>α</i>-glucosidase) and 14.30 to 41.50 (urease). Compounds <b>6</b>, <b>7</b>, <b>14</b>, and <b>12</b>, with IC<sub>50</sub> values of 2.50, 3.20, 3.40, and 3.50 μM as compared to standard acarbose (IC<sub>50</sub> = 5.30 µM), while the same compounds showed 14.30, 19.20, 21.80, and 22.30 comparable with thiourea (IC<sub>50</sub> = 31.40 μM), respectively, showed excellent inhibitory activity. The structure−activity relationship revealed that the size and electron-donating or electron-withdrawing effects of substituents influenced the enzymatic activities such as α-glucosidase and urease. Compound <b>6</b> was a dual potent inhibitor against <i>α</i>-glucosidase and urease due to the presence of -CF<sub>3</sub> electron-withdrawing functionality on the phenyl ring. To the best of our knowledge, these synthetic compounds were found to be the most potent dual inhibitors of α-glucosidase and urease with minimum IC<sub>50</sub> values. Moreover, in silico studies on most active compounds, i.e., <b>6</b>, <b>7</b>, <b>14</b>, and <b>12</b>, were also performed to understand the binding interaction of most active compounds with active sites of α-glucosidase and urease enzymes. |
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| Item Description: | 10.3390/ph16121650 1424-8247 |