A simple and efficient synthesis of benzimidazoles containing piperazine or morpholine skeleton at C-6 position as glucosidase inhibitors with antioxidant activity

Ozil M., Parlak C., Baltas N.

BIOORGANIC CHEMISTRY, cilt.76, ss.468-477, 2018 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 76
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1016/j.bioorg.2017.12.019
  • Dergi Adı: BIOORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.468-477
  • Anahtar Kelimeler: Benzimidazole, Microwave, alpha-Glucosidase, Antioxidant, Structure-activity relationship (SAR), Synthesis, MOLECULAR DOCKING, BIOLOGICAL EVALUATION, DERIVATIVES, DISEASE, DESIGN
  • Recep Tayyip Erdoğan Üniversitesi Adresli: Evet

Özet

A novel 2-(aryl)-6-morpholin-4-yl(or 4-methylpiperazin-1-yl)-1H-benzimidazole derivatives were designed and expeditiously synthesized starting from 5-morpholin-4-yl(or 4-methylpiperazin-1-yl)-2-nitroaniline with various aldehydes which were preliminarily screened for in vitro antioxidant activities and glucosidase inhibitors. The benzimidazoles were effectively synthesized by a rapid 'onepot' nitro reductive cyclization reaction using sodium hydrosulfite as a reagent. All reactions were conducted using both the microwave and conventional methods to compare yields and reaction times. Antioxidant activities of the synthesized compounds were clarified using various in vitro antioxidant assays including Cupric Reducing Antioxidant Capacity (CUPRAC, ranging from 5.511 to 19.703 mM Trolox/mg compound) and Ferric Reducing Antioxidant Power (FRAP) (1.141-12.943 mM FeSO4 center dot 7H(2)O/mg compound) assays. Also, the radical scavenging activities of these compounds were assayed using ABTS(center dot+) and DPPH center dot methods. The results showed that all compounds exhibited very high scavenging activity. These synthesized compounds were then evaluated for their a-glucosidase inhibitory potential and seven compounds demonstrated an inhibitory potential much better than the standard acarbose. Herein, we will provide details of the structure activity relationship of the benzimidazole analog for the potency. (C) 2017 Elsevier Inc. All rights reserved.