Design, synthesis, antioxidant, and anti-breast cancer activities of novel diethyl(alkyl/aryl/heteroarylamino)(4-(pyridin-2-yl)phenyl)methylphosphonates

Arch Pharm (Weinheim). 2013 May;346(5):380-91. doi: 10.1002/ardp.201300032. Epub 2013 Apr 16.

Abstract

A series of new diethyl(alkyl/aryl/heteroarylamino)(4-(pyridine-2-yl)phenyl)methylphosphonates (4a-t) were synthesized via three-component Kabachnik-Field's reaction of 4-(pyridin-2-yl)benzaldehyde, diethylphosphite and various primary amines, catalyzed by cupric acetate monohydrate [Cu(OAc)(2) ∙ H(2)O] under solvent-free and microwave irradiation conditions. Their computational docking analysis supported them as good therapeutic agents to the breast cancer aromatase enzyme and ascertained 4a, 4h, 4m, 4n, and 4t as potential molecules with good binding affinities varying from -9.0 to -9.6 kcal/mol and containing the 4-(pyridine-2-yl)phenyl moiety as a pharmacophore. Their in vitro screening performed for the anti-cell proliferation activity against MBC-MCF7 cells by MTT and Trypan blue assays confirmed 4m, 4n, and 4q as promising compounds to sustain a low percentage of cell viability at 20 µg/mL concentration. These compounds were also evaluated for their antioxidant activity by the DPPH method and the results established that compounds 4m, 4n, and 4q show around 10% higher activity than the standard antioxidant ascorbic acid.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Ascorbic Acid / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Female
  • Humans
  • MCF-7 Cells
  • Molecular Docking Simulation
  • Organophosphonates / chemical synthesis
  • Organophosphonates / chemistry
  • Organophosphonates / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Organophosphonates
  • Ascorbic Acid