Synthesis and in Silico Docking Studies of Ethyl 2‐(2‐Arylidene‐1‐alkylhydrazinyl)thiazole‐4‐carboxylates as Antiglycating Agents

Abstract

Ethyl 2-(2-arylidene-1-alkylhydrazinyl)thiazole-4-carboxylates (1a -k) were synthesized by alkylation on HN-of ethyl 2-(2-arylidenehydrazinyl)thiazole-4-carboxylates. The proposed structures (1a -k) are corroborated by spectro-analytical techniques like UV, FT-IR, 1 H-, 13 C-NMR and HR-MS. All synthesized compounds were screened for their antiglycation and antioxidant assays. The in vitro antiglycation results revealed promising activity of compounds 1a, 1b, 1d, 1e, 1f, 1g, 1j and 1k with IC 50 values 0.0004 � 1.097-17.22 � 0.538 μM when compared to standard, aminoguanidine (IC 50 = 25.50 � 0.337 μM). Among all tested compounds 1j and 1k are the best antiglycating agents with IC 50 values 1.848 � 0.646 and 0.0004 � 1.097 μM, respectively. The in-silico studies also agree with these results where binding energy for 1j and 1k was found to be À 9.25 and À 8.42 kcal/mol with calculated dissociation constants of 0.16 and 0.67 μM, respectively. The antiglycation results demonstrate the application of these compounds in reducing diabetic complications.

Synthesis of Thiazole‐Chalcone Hybrid Molecules: Antioxidant, Alpha(α)‐Amylase Inhibition and Docking Studies

“…Finally, the results of the elemental analysis were assessed, and it was seen that the calculated values were near to the found values. All spectroscopic data is consistent with our previous related research [52–62] …”

Synthesis of Fluorinated Hydrazinylthiazole Derivatives: A Virtual and Experimental Approach to Diabetes Management

“…HAS has multiple glycation sites (F1−9) in its three domains. 39,40 6). These ligands form π−π stacking interactions with Tyr 138 and show interactions with Lys 137 , one of the main residues that undergo glycation.…”

“…Here, we have performed antiglycation studies for the synthesized ligands ( 3a – o ) using the HSA three-dimensional structure as a target protein. HAS has multiple glycation sites (F1–9) in its three domains. , Sudlow site II is a fatty acid binding site mainly consisting of Leu 115 , Pro 118 , Met 123 , Ala 126 , Phe 134 , Lys 137 , Tyr 138 , Glu 141 , Ile 142 , His 146 , Phe 149 , Leu 154 , Phe 157 , Tyr 161 , Leu 185 , Arg 186 , Gly 189 , Lys 190 , and Ser 193 amino acids. The ligand 3a shows binding to the same Sudlow site II with a binding energy of −9.54 kcal/mol and a binding constant of 102 nM (Table ).…”

“…Recently, Shahzadi et al reported the antiglycation potential of alkyl-based hydrazinylthiazoles . Compounds I and II (Figure ) were highlighted as excellent antiglycating agents with IC 50 values of 1.848 ± 0.646 and 0.0004 ± 1.097 μM, respectively (amino guanidine, IC 50 = 25.50 ± 0.337 μM).…”

“…Recently, Shahzadi et al reported the antiglycation potential of alkyl-based hydrazinylthiazoles. 29 Compounds I and II ( Figure 4 ) were highlighted as excellent antiglycating agents with IC 50 values of 1.848 ± 0.646 and 0.0004 ± 1.097 μM, respectively (amino guanidine, IC 50 = 25.50 ± 0.337 μM). In addition, Hasnain et al reported the syntheses of two series of hydrazinylthiazoles and evaluated their antiglycation and α-amylase inhibition potential.…”