Design, Synthesis, and In Silico Molecular Docking Studies of Adamantanyl Hydrazinylthiazoles as Potential...

Diabetes mellitus (DM) is a widespread disease that poses a major threat to millions of people. To address this issue, we have synthesized seventeen new 4-(adamantan-1-yl)-(2-(arylidene)hydrazinyl)thiazoles (3a-q) via Hantzsch synthetic approach. The molecular structures of all the compounds were confirmed using FT-IR, ¹H- and ¹³C-NMR spectroscopy, and HR-mass spectrometry. Protein kinase, α-amylase, glycation, and oxidation inhibition potential of all compounds were also investigated, and it was found that compounds 3b, 3c, 3e-3g, and 3i-3q have shown excellent α-amylase inhibition (IC₅₀ = 7.91 ± 0.07 to 28.57 ± 0.1 µM), compounds 3c, 3e, 3i, 3k, and 3p (IC₅₀ = 30.6 ± 0.06 to 37.8 ± 0.005 ppm) were found to be highly potent anti-glycating agents, and compounds 3c, 3g, 3h, 3k, and 3m were found to be more potent protein kinase inhibitors as compared to standards. The compounds 3b, 3c, 3d, 3e, 3f, 3g, 3i, 3k, 3l, 3m, 3n, 3p, and 3q have shown good antioxidant potential (IC₅₀ = 27.5 ± 0.09 to 48.8 ± 0.09 µM) as compared to standard ascorbic acid (IC₅₀ = 51.3 ± 0.1 µM). The biocompatibility of all samples was also tested by employing brine shrimp lethality and in vitro hemolytic assays and was found to be safe to human erythrocytes at tested concentrations. Furthermore, the molecular docking simulation study also revealed that almost all synthesized compounds have potential interactions with target proteins at the molecular level.