Halogenated naphthochalcones and structurally related naphthopyrazolines with antitumor activity

Bioorg Med Chem Lett. 2016 Nov 1;26(21):5168-5171. doi: 10.1016/j.bmcl.2016.09.076. Epub 2016 Sep 30.

Abstract

Three 3-(3-halo-4,5-dimethoxyphenyl)-1-(2-naphthyl)prop-2-en-1-ones 1 and three structurally related 2-pyrazolines 2 were prepared and assessed in vitro for anticancer activity. The chalcones 1 were antiproliferative with low double-digit micromolar IC50 values against six tumor cell lines whereas the pyrazolines 2 showed low single-digit micromolar IC50 values against this panel. The pyrazolines inhibited ATP-binding cassette efflux transporters of types P-gp and BCRP while the chalcones inhibited selectively BCRP. All test compounds induced an accumulation of HT-29 colon carcinoma cells in the G2/M phase of the cell cycle and they interfered with the microtubule and F-actin dynamics, but only the chalcones induced apoptosis in 518A2 melanoma cells after 24h.

Keywords: BCRP; Chalcones; P-gp; Pyrazolines; TUNEL.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Chalcones / chemistry*
  • Chalcones / pharmacology
  • DNA, Neoplasm / drug effects
  • Drug Screening Assays, Antitumor
  • Halogens / chemistry*
  • Humans
  • Inhibitory Concentration 50
  • Naphthalenes / chemistry*
  • Pyrazoles / chemistry*
  • Pyrazoles / pharmacology

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Chalcones
  • DNA, Neoplasm
  • Halogens
  • Naphthalenes
  • Pyrazoles