4-Adamantyl-(2-(arylidene)hydrazinyl)thiazoles As Potential Antidiabetic Agents: Experimental and Docking Studies

Abstract

Aim: To develop an efficient and cost-effective antidiabetic agent. Methods: A simple and convenient Hantzsch synthetic strategy was used to prepare 4-adamantyl-(2-(arylidene)hydrazinyl)thiazoles. Results: Fifteen newly established structures of 4-adamantyl-(2-(arylidene)hydrazinyl)thiazoles were tested for their α-amylase, antiglycation and antioxidant activities. Almost all tested compounds showed excellent α-amylase inhibition. Compounds 3a and 3j exhibited the highest potency, with IC₅₀ values of 16.34 ± 2.67 and 16.64 ± 1.12 μM, respectively. Compounds 3c and 3i exhibited comparable antiglycation potential with the standard, aminoguanidine. The antioxidant potential of compound 3g was found to be excellent, with an IC₅₀ value of 28.19 ± 0.2563 μM. The binding interactions of compound 3a (binding energy = -8.833 kcal/mol) with human pancreatic α-amylase identified 3a as a potent α-amylase inhibitor. Conclusion: Enrichment of established structures with more electron-donating functionalities may assist/lead to the development of more potent antidiabetic drugs.

Plain language summary

Diabetes is one of the major causes of death in the present era. To combat damaging processes associated with diabetes, called glycation and oxidation, we prepared a series of compounds called 4-adamantyl-(2-(arylidene)hydrazinyl)thiazoles. The established structures were tested for their antidiabetic potential. The compounds 4-adamantyl-(2-(4-chlorobenzylidene)hydrazinyl)thiazole and 4-adamantyl-(2-(2-chlorobenzylidene)hydrazinyl)thiazole showed the highest potency. The compounds 4-adamantyl-(2-(4-bromobenzylidene)hydrazinyl)thiazole and 4-adamantyl-(2-(2-hydroxybenzylidene)hydrazinyl)thiazole exhibited comparable antiglycation potential. The antioxidant potential of compound 4-adamantyl-(2-(3-nitrobenzylidene)hydrazinyl)thiazole was found to be excellent. A further test was used to check toxicity and all compounds were found to be biocompatible. We also investigated, through docking studies, the way in which these compounds interact with the human proteins albumin and pancreatic α-amylase.

Tweetable abstract

Novel adamantylhydrazinylthiazoles were prepared, characterized and evaluated for their antiglycation/antioxidant potential and amylase inhibition. Cytotoxicity of the compounds was checked and molecular docking was performed to check their binding interactions with HSA and HPA.

Graphical abstract

Keywords:

• adamantane
• α-amylase
• antiglycation
• antioxidant
• hemolysis
• molecular docking
• thiazoles

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184

Author contributions

Y Iqbal: performed all experimental work and characterization and write-up. M Haroon: data compilation, assisting synthesis and write-up. T Akhtar: supervised the first author, designed the project, refined the paper and is corresponding author. T Nizami and H Mehmood: assisted the first author (characterization). E Tahir and M Ehsan: molecular docking studies and writing of that part of the paper.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.