Visible light-controlled carbon monoxide delivery combined with the inhibitory activity of histone deacetylases from a manganese complex for an enhanced antitumor therapy

J Inorg Biochem. 2021 Mar:216:111354. doi: 10.1016/j.jinorgbio.2021.111354. Epub 2021 Jan 8.

Abstract

Multifunctional drugs with synergistic effects have been widely developed to enhance the treatment efficiency of various diseases, such as malignant tumors. Herein, a novel bifunctional manganese(I)-based prodrug [MnBr(CO)3(APIPB)] (APIPB = N-(2-aminophen-yl)-4-(1H-imidazo[4,5-f] [1, 10] phenanthrolin-2-yl)benzamide) with inhibitory histone deacetylase (HDAC) activity and light-controlled carbon monoxide (CO) delivery was successfully designed and synthesized. [MnBr(CO)3(APIPB)] readily released CO under visible light irradiation (λ > 400 nm) through which the amount of released CO could be controlled by manipulating light power density and illumination time. In the absence of light irradiation, the cytotoxic effect of [MnBr(CO)3(APIPB)] on cancer cells was greater than that of the commercially available HDAC inhibitor MS-275. Consequently, with a combination of CO delivery and HDAC inhibitory activity, [MnBr(CO)3(APIPB)] showed a remarkably enhanced antitumor effect on HeLa cells (IC50 = 3.2 μM) under visible light irradiation. Therefore, this approach shows potential for the development of medicinal metal complexes for combined antitumor therapies.

Keywords: Carbon monoxide; Combined therapy; Histone deacetylase inhibitor; Light-controlled release; Manganese carbonyl complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents*
  • Carbon Monoxide* / chemistry
  • Carbon Monoxide* / pharmacokinetics
  • Carbon Monoxide* / pharmacology
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacokinetics
  • Coordination Complexes / pharmacology
  • HeLa Cells
  • Histone Deacetylase Inhibitors* / chemistry
  • Histone Deacetylase Inhibitors* / pharmacokinetics
  • Histone Deacetylase Inhibitors* / pharmacology
  • Humans
  • Light*
  • Manganese* / chemistry
  • Manganese* / pharmacokinetics
  • Manganese* / pharmacology
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / pathology
  • Prodrugs* / chemistry
  • Prodrugs* / pharmacokinetics
  • Prodrugs* / pharmacology

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Histone Deacetylase Inhibitors
  • Prodrugs
  • Manganese
  • Carbon Monoxide