Multi-target 1,4-dihydropyridines showing calcium channel blockade and antioxidant capacity for Alzheimer's disease therapy

Bioorg Chem. 2019 Oct:91:103205. doi: 10.1016/j.bioorg.2019.103205. Epub 2019 Aug 16.

Abstract

In this work we describe the synthesis, Ca+2 channel blockade capacity and antioxidant power of N3,N5-bis(2-(5-methoxy-1H-indol-3-yl)ethyl)-2,6-dimethyl-4-aryl-1,4-dihydropyridine-3,5-dicarboxamides 1-9, a number of multi-target small 1,4-dihydropyridines (DHP), designed by juxtaposition of melatonin and nimodipine. As a result, we have identified antioxidant DHP 7 (Ca2+ channel blockade: 55%, and 8.78 Trolox/Equivalents), the most balanced DHP analyzed here, for potential Alzheimer's disease therapy.

Keywords: 1,4-Dihydropyridines; Alzheimer’s disease; Antioxidants; Calcium channel blockers; Hantzsch multicomponent reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Antioxidants / pharmacology*
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / chemistry*
  • Dihydropyridines / pharmacology*
  • Humans
  • Melatonin / pharmacology
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / pathology
  • Nimodipine / pharmacology
  • Tumor Cells, Cultured

Substances

  • Antioxidants
  • Calcium Channel Blockers
  • Calcium Channels
  • Dihydropyridines
  • Nimodipine
  • 1,4-dihydropyridine
  • Melatonin
  • Calcium