Synthesis and Antioxidant Activity of New Selenium-Containing Quinolines

Med Chem. 2021;17(6):667-676. doi: 10.2174/1573406416666200403081831.

Abstract

Background: Quinoline derivatives have been attracted much attention in drug discovery, and synthetic derivatives of these scaffolds present a range of pharmacological activities. Therefore, organoselenium compounds are valuable scaffolds in organic synthesis because of their pharmacological activities and their use as versatile building blocks for regio-, chemo-and stereoselective reactions. Thus, the synthesis of selenium-containing quinolines has great significance, and their applicability range from simple antioxidant agents, to selective DNA-binding and photocleaving agents.

Objective: In the present study, we describe the synthesis and antioxidant activity in vitro of new 7- chloro-N(arylselanyl)quinolin-4-amines 5 by the reaction of 4,7-dichloroquinoline 4 with (arylselanyl)- amines 3.

Methods: For the synthesis of 7-chloro-N(arylselanyl)quinolin-4-amines 5, we performed the reaction of (arylselanyl)-amines 3 with 4,7-dichloroquinoline 4 in the presence of Et3N at 120 °C in a sealed tube. The antioxidant activities of the compounds 5 were evaluated by the following in vitro assays: 2,2- diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, 2,2-azinobis-3- ethylbenzothiazoline-6-sulfonic acid (ABTS), ferric ion reducing antioxidant power (FRAP), nitric oxide (NO) scavenging and superoxide dismutase-like activity (SOD-Like).

Results: 7-Chloro-N(arylselanyl)quinolin-4-amines 5a-d have been synthesized in yields ranging from 68% to 82% by the reaction of 4,7-dichloroquinoline 4 with arylselanyl-amines 3a-d using Et3N as a base, at 120 °C, in a sealed tube for 24 hours and tolerates different substituents, such as -OMe and -Cl, in the arylselanyl moiety. The obtained compounds 5a-d presented significant results concerning the antioxidant potential, which had an effect in the tests of inhibition of radical's DPPH, ABTS+ and NO, as well as in the analysis that evaluates the capacity (FRAP) and in the superoxide dismutase-like activity assay (SOD-Like). It is worth mentioning that 7-chloro- N(arylselanyl)quinolin-4-amine 5b presented excellent results, demonstrating a better antioxidant capacity when compared to the others.

Conclusion: According to the obtained results, 7-chloro-N(arylselanyl)quinolin-4-amines 5 were synthesized in good yields by the reaction of 4,7-dichloroquinoline with arylselanyl-amines and tolerated different substituents in the arylselanyl moiety. The tested compounds presented significant antioxidant potential in the tests of inhibition of DPPH, ABTS+, and NO radicals, as well as in the FRAP and superoxide dismutase-like activity assays (SOD-Like).

Keywords: Synthesis; amines; antioxidant; quinolines; radicals; selenium.

MeSH terms

  • Amines / chemistry
  • Antioxidants / chemical synthesis*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Benzothiazoles / chemistry
  • Chemistry Techniques, Synthetic
  • Nitric Oxide / chemistry
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Selenium / chemistry*
  • Sulfonic Acids / chemistry

Substances

  • Amines
  • Antioxidants
  • Benzothiazoles
  • Quinolines
  • Sulfonic Acids
  • 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid
  • Nitric Oxide
  • Selenium