Prenylated Coumarins from the Fruits of Manilkara zapota with Potential Anti-inflammatory Effects and Anti-HIV Activities

J Agric Food Chem. 2019 Oct 30;67(43):11942-11947. doi: 10.1021/acs.jafc.9b04326. Epub 2019 Oct 17.


Manilkara zapota, usually known as Sapodilla, is a fairly slow-growing evergreen tropical tree which belongs to the genus Manilkara (Sapotaceae), indigenous to Central America, southern Mexico, and the Caribbean. The ripe fruits of M. zapota have been widely consumed as an uniquely flavored tropical fruit and verified to hold a variety of health benefits. In order to investigate the potential health-promoting chemical compositions from the fruits of M. zapota cultivated in Hainan Island of China, a systematic and in-depth phytochemical study on this fruit was accordingly implemented. In our current study, three new prenylated coumarins, manizapotins A-C (1-3), together with seven known prenylated coumarins (4-10), were separated from the fruits of M. zapota. The chemical structures of new prenylated coumarins 1-3 were unambiguously established by means of comprehensive spectroscopic analyses, and the known compounds 4-10 were determined by comparing their experimental spectral data with those described data in the literature. This is the first time to discover prenylated coumarins occurring in M. zapota. The potential anti-inflammatory effects and anti-HIV (human immunodeficiency virus) activities of all these separated prenylated coumarins were assessed. Prenylated coumarins 1-10 dispalyed remarkable inhibitory effects against nitric oxide production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells with the IC50 values equivalent to that of hydrocortisone in vitro. Meanwhile, prenylated coumarins 1-10 exhibited pronounced anti-HIV-1 reverse transcriptase activities with the EC50 values in range of 0.12-8.69 μM. These results suggest that appropriate and reasonable consumption of the fruits of M. zapota might assist people to prevent and reduce the occurrence of inflammatory diseases together with the infection of HIV. Furthermore, the discovery of these prenylated coumarins from the fruits of M. zapota holding pronounced anti-inflammatory effects along with anti-HIV activities could be of great significance to the research and development of new natural anti-inflammatory and anti-HIV agents.

Keywords: Manilkara zapota; anti-HIV activity; anti-inflammatory effect; manizapotins A−C; prenylated coumarins.

MeSH terms

  • Animals
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / isolation & purification
  • Anti-HIV Agents / pharmacology
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology
  • China
  • Coumarins / chemistry*
  • Coumarins / isolation & purification
  • Coumarins / pharmacology
  • Fruit / chemistry
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Manilkara / chemistry*
  • Mice
  • Molecular Structure
  • Plant Extracts / chemistry*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Prenylation
  • RAW 264.7 Cells


  • Anti-HIV Agents
  • Anti-Inflammatory Agents
  • Coumarins
  • Plant Extracts
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase