Antineoplastic Constituents from the Chemical Diversified Extract of Radix puerariae

Chem Biodivers. 2019 Jan;16(1):e1800408. doi: 10.1002/cbdv.201800408. Epub 2018 Dec 28.

Abstract

To enhance the structural diversity of isoflavonoids and provide more derivatives for the biological screening, a semisynthetic mixture was generated by diversification of the crude extract of Radix puerariae (Pueraria montana var. lobata) through the chemical reaction with hydrazine hydrate. Eleven 3,4-diarylpyrazoles (1-11) and two 5-phenyl-6-benzyldihydropyridazinones (12 and 13) were isolated from the semisynthetic mixture, and their structures were identified by spectroscopic methods in combination with X-ray crystallographic analysis. Among them, nine compounds (5-13) were new derivatives. All the compounds were evaluated on the inhibitory activities against the prostate cancer cell lines LNCaP and PC3. Compounds 12 and 13 were found to exhibit much more potent inhibitory activities against the androgen dependent LNCaP cells than the androgen independent PC3 cells. Rapid synthesis of new 3,4-diarylpyrazoles and two 5-phenyl-6-benzyldihydropyridazinones with significant biological activity highlights the great potential of one-pot combinatorial modification for the diversification of natural products.

Keywords: Pueraria montana var. lobatea; Radix puerariae; antineoplastic activity; biological activity; natural products; semisynthetic.

MeSH terms

  • Androgens / physiology
  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Biological Products / chemistry
  • Biological Products / isolation & purification
  • Biological Products / pharmacology
  • Carbon-13 Magnetic Resonance Spectroscopy
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Drug Screening Assays, Antitumor
  • Humans
  • Male
  • Molecular Structure
  • Plant Extracts / chemistry*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Roots / chemistry*
  • Prostatic Neoplasms / pathology
  • Proton Magnetic Resonance Spectroscopy
  • Pueraria / chemistry*
  • Pyrazoles / chemistry
  • Pyrazoles / isolation & purification
  • Pyrazoles / pharmacology
  • Pyrimidines / chemistry
  • Pyrimidines / isolation & purification
  • Pyrimidines / pharmacology
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • Androgens
  • Antineoplastic Agents, Phytogenic
  • Biological Products
  • Plant Extracts
  • Pyrazoles
  • Pyrimidines