Aromatase Inhibitory Activity of Geranylated Coumarins, Mammeasins C and D, Isolated from the Flowers of Mammea siamensis

Chem Pharm Bull (Tokyo). 2016;64(7):880-5. doi: 10.1248/cpb.c16-00218.

Abstract

A methanol extract of the flowers of Mammea siamensis (Calophyllaceae) was found to inhibit enzymatic activity against aromatase (IC50=16.5 µg/mL). From the extract, two new geranylated coumarins, mammeasins C (1) and D (2), were isolated together with seven coumarins: 8-hydroxy-5-methyl-7-(3,7-dimethyl-octa-2,6-dienyl)-9-(2-methyl-1-oxobutyl)-4,5-dihydropyrano[4,3,2-de]chromen-2-one (9), 8-hydroxy-5-methyl-7-(3,7-dimethyl-octa-2,6-dienyl)-9-(3-methyl-1-oxobutyl)-4,5-dihydropyrano[4,3,2-de]chromen-2-one (10), mammeas A/AA (14), A/AB (15), A/AA cyclo D (18), E/BA (23), and E/BC cyclo D (25). The structures of 1 and 2 were elucidated on the basis of spectroscopic evidence. Among the isolates including 17 previously reported coumarins, 1 (IC50=2.7 µM), 2 (3.6 µM), and mammea B/AB cyclo D (21, 3.1 µM) showed relatively strong inhibitory activities comparable to the activity of the synthetic nonsteroidal aromatase inhibitor aminoglutethimide (2.0 µM).

MeSH terms

  • Aromatase / metabolism*
  • Aromatase Inhibitors / chemistry
  • Aromatase Inhibitors / isolation & purification
  • Aromatase Inhibitors / pharmacology*
  • Coumarins / chemistry
  • Coumarins / isolation & purification
  • Coumarins / pharmacology*
  • Dose-Response Relationship, Drug
  • Flowers / chemistry*
  • Humans
  • Mammea / chemistry*
  • Molecular Structure
  • Recombinant Proteins / metabolism
  • Structure-Activity Relationship

Substances

  • Aromatase Inhibitors
  • Coumarins
  • Recombinant Proteins
  • mammeasin C
  • mammeasin D
  • Aromatase