Mercaptobenzimidazole-Based 1,3-Thaizolidin-4-ones as Antidiabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition Activity, and Molecular Docking Studies

Abstract

In this research work, we have focused our efforts to synthesize a series of 2-mercaptobenzimidazole-based 1,3-thiazolidin-4-ones ( 5–24 ) following a multistep reaction strategy and characterization of the synthesized derivatives with the help of various spectroscopic techniques. To find the antidiabetic potentials of the synthesized compounds ( 5–24 ), in vitro alpha-glucosidase inhibitory activity was performed using acarbose (IC 50 = 873 ± 1.2 μM) as the reference standard. The results of the antidiabetic assay were very encouraging because compounds 5 , 8 , and 14 showed excellent inhibitions with IC 50 values of 5.22 ± 0.14, 5.69 ± 0.10, and 10.20 ± 0.12 μM, respectively. The experimental results of anti-alpha-glucosidase activity prompted us to investigate and propose a possible mechanism of how the active molecules will interact with the target enzyme. For this purpose, molecular docking with the AutoDock Vina (an open-source and reliable docking platform) gave us an insight into the binding interactions of the active compounds to different amino acid residues of the enzyme.

Molecular insights into α‐glucosidase inhibition and antiglycation properties affected by the galloyl moiety in (−)‐epigallocatechin‐3‐gallate

“…Figure 4(B) shows the results of the Ramachandran plot for the ⊍-glucosidase protein obtained from homology modeling. 45 Supporting Information Table S1 summarizes the molecular docking energy scoring of the EGC and EGCG compounds with the ⊍-glucosidase protein and the predicted inhibitory activity values (K i ). The experimental binding energies obtained through calculation and the theoretical docking binding energies obtained through molecular docking are presented in Table 1 and Table S1, respectively.…”

Thiazolidinone‐Heterocycle Frameworks: A Concise Review of Their Pharmacological Significance

“…Synthesis of mercaptobenzimidazole‐Based 1,3‐Thaizolidin‐4‐ones derivatives 30 and antidiabetic evaluation via alpha‐glucosidase inhibitory assay have been reported by Khan et al. [51] . Among the synthesized compounds 30 a displayed the highest degree of inhibition against alpha‐glucosidase enzyme with an IC 50 value of 5.22 μM which was 167‐fold more active than the standard acarbose which displayed an IC 50 value of 873 μM (Figure 30), respectively.…”

“…Synthesis of mercaptobenzimidazole-Based 1,3-Thaizolidin-4-ones derivatives 30 and antidiabetic evaluation via alphaglucosidase inhibitory assay have been reported by Khan et al. [51] Among the synthesized compounds 30 a displayed the highest degree of inhibition against alpha-glucosidase enzyme with an IC 50 value of 5.22 μM which was 167-fold more active than the standard acarbose which displayed an IC 50 value of 873 μM (Figure 30), respectively. Moreover, molecular docking in the active gorge of homology-modelled alpha-glucosidase revealed that compound 30 a formed various interactions with various active site amino acid residues which could explain the observed activity.…”

Synthesis of new diphenyl urea-clubbed imine analogs and its Implications in diabetic management through in vitro and in silico approaches

“…A crucial strategy for avoiding type II diabetes mellitus' deadly effects is to control blood glucose levels. Hence, there is an immense need to synthesize new small molecules and to evaluate their anti-diabetic potential against α-glucosidase, might be used as drug candidates for the treatment of type II diabetes mellitus [5][6][7][8][9] . Several therapeutic approaches of diabetes are available,…”

“…The docking results of compounds 3a-3y.CH 3 ), 3.74 (s,3H, CH 3 ), 6.77-6.82 (m,2H),6.86(d,1H, J = 7.8 Hz),6.89(d,1H, J = 10.2 Hz), 6.97(d,1H, J = 7.8 Hz), 7.02(t,1H, J = 7.8 Hz), 7.04-7.07 (m,2H), 7.23-7.26 (m,2H), 7.63(s,1H),7.79(s,1H), 8.31(d,1H, J = 7.8 Hz),8.46(s, 1H),13.051(s,1H); 13 C-NMR δppm; 21.74, 55.7, 114.7, 116.9, 118.6, 119.0, 119.3, 120.3, 120.6, 122.8, 123.9, 127.9, 128.7, 133.0, 138.1, 138.4, 138.8, 148.0, 150.2, 152.8, 164.2; C 22 H 21 N 3 O 3 (375.43) m/z (%): 376.16[M + H] + (100). Hz), 7.31 (d,2H, J = 7.8 Hz), 7.49 (d,3H, J = 7.2 Hz), 7.70 (d,1H, J = 7.2 Hz), 8.22 (d,1H, J = 8.4 Hz),8.46(s,1H),8.60 (s,1H),9.74 (s,1H), 9.80(s,1H); 13 C-NMR ppm; 55.8,111.8, 115.5,117.1,118.3,119.7,122.0, 124.5, 126.4,127.9,128.7, 134.1,138.7,138.8,148.0,150.6,152.1,159.6; C 21 H 18 ClN 3 O 3 (395.84) m/z (%): 396.10[M + H] + (100).…”