Carbazole alkaloids with potential cytotoxic activities targeted on PCK2 protein from Murraya microphylla

Bioorg Chem. 2021 Sep:114:105113. doi: 10.1016/j.bioorg.2021.105113. Epub 2021 Jun 21.

Abstract

From the 95% aqueous ethanol extract of Murraya microphylla, five pairs of new carbazole alkaloid enantiomers, (+/-)-microphylines N-R (1a/1b-5a/5b), were isolated, together with 20 known carbazole alkaloids. The structures of the new compounds were determined by the HRMS and NMR spectroscopic data, along with the calculated electronic circular dichroism (ECD) and Mo2(AcO)4-induced CD data. The known compound (+)-mahanine (21) showed significant cytotoxicities against Du145, HepG2, HeLa, and HCT-116 cell lines, and its possible mechanism was deduced to target on phosphoenolpyruvate carboxykinase 2 (PCK2) protein via surface plasmon resonance (SPR) and molecular docking.

Keywords: Carbazole alkaloid enantiomers; Cytotoxicities; Murraya microphylla (Merr. et Chun) Swing; PCK2 protein; Rutaceae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry
  • Alkaloids / isolation & purification
  • Alkaloids / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Carbazoles / chemistry
  • Carbazoles / isolation & purification
  • Carbazoles / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Docking Simulation
  • Molecular Structure
  • Murraya / chemistry*
  • Phosphoenolpyruvate Carboxykinase (ATP) / antagonists & inhibitors*
  • Phosphoenolpyruvate Carboxykinase (ATP) / metabolism
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Carbazoles
  • Enzyme Inhibitors
  • carbazole
  • PCK2 protein, human
  • Phosphoenolpyruvate Carboxykinase (ATP)