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Synthesis of Novel Bi-Heterocycles as Valuable Anti-Diabetic Agents: 2-({5-((2-Amino-1,3-Thiazol-4-yl)methyl)-1,3,4-Oxadiazol-2-yl}sulfanyl)-N-(Substituted)acetamides

Abstract

The synthesis of a new series of S-substituted acetamides derivatives of 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol were synthesized and evaluated for enzyme inhibition study along with cytotoxic behavior. Ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate was converted to corresponding acid hydrazide by hydrazine hydrate in ethanol. The reflux of acid hydrazide with carbon disulfide resulted to 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol. Different electrophiles were synthesized by the reaction of respective anilines (one in each reaction) and 2-bromoacetylbromide in an aqueous medium. The targeted bi-heterocyclic compounds were synthesized by stirring nucleophilic 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol with different acetamides electrophiles (one after another), in DMF using LiH as base and activator. The proposed structures of newly synthesized compounds were deduced by spectroscopic techniques such as 1H NMR, 13C NMR, EI MS and elemental analysis. These novel bi-heterocycles were tested for their anti-diabetic potential via the in vitro inhibition of \(\alpha \)-glucosidase enzyme. The in silico study of these molecules was also coherent with their enzyme inhibition data. Furthermore, these molecules were analyzed for their cytotoxic behavior against brine shrimps. It was inferred from the results that most of them exhibited very potent inhibitory potential against the studied enzyme and can be utilized as valuable anti-diabetic agent.

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FUNDING

The Higher Education Commission (HEC) of Pakistan is highly acknowledged by the authors for financial support regarding purchasing of chemicals and spectral study.

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Correspondence to Muhammad Athar Abbasi.

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This article does not contain any studies involving animals or human participants performed by any of the authors.

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Corresponding author: phone: (+92)-42-111000010; e-mail: atrabbasi@yahoo.com; abbasi@gcu.edu.pk

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Muhammad Athar Abbasi, Ramzan, M.S., Aziz-ur-Rehman et al. Synthesis of Novel Bi-Heterocycles as Valuable Anti-Diabetic Agents: 2-({5-((2-Amino-1,3-Thiazol-4-yl)methyl)-1,3,4-Oxadiazol-2-yl}sulfanyl)-N-(Substituted)acetamides. Russ J Bioorg Chem 46, 590–598 (2020). https://doi.org/10.1134/S1068162020040020

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  • DOI: https://doi.org/10.1134/S1068162020040020

Keywords

  • : ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate
  • 1,3,4-oxadiazole
  • acetamide
  • enzyme inhibition
  • molecular docking
  • cytotoxicity