Synthesis of thiocolchicine amine derivatives and evaluation of their antiproliferative activity

Bioorg Med Chem Lett. 2021 Nov 15:52:128382. doi: 10.1016/j.bmcl.2021.128382. Epub 2021 Sep 27.

Abstract

A series of 22 amine analogs of thiocolchicine were synthesized using the reductive amination reaction. The antiproliferative activities of these compounds were tested against four tumor cell lines as well as one normal cell line. The tested analogs exhibited IC50 values in the nanomolar range accompanied by high selectivity indexes, and most importantly, they were able to break the drug resistance of the human colon adenocarcinoma resistant cell line (LoVo/DX). Also, a correlation between the antiproliferative activity and physicochemical properties of the novel compounds has been found.

Keywords: Antiproliferative activity; Colchicine analogs; Natural products; Reductive amination; Structure–activity relationship; Thiocolchicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Amines / chemical synthesis
  • Amines / chemistry
  • Amines / pharmacology*
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colchicine / analogs & derivatives*
  • Colchicine / chemical synthesis
  • Colchicine / chemistry
  • Colchicine / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Amines
  • Antineoplastic Agents
  • thiocholchicine
  • Colchicine