Phytochemicals with Chemopreventive Activity Obtained from the Thai Medicinal Plant Mammea siamensis (Miq.) T. Anders.: Isolation and Structure Determination of New Prenylcoumarins with Inhibitory Activity against Aromatase

  • Int J Mol Sci. 2022 Sep 23;23(19):11233. doi: 10.3390/ijms231911233.
Fenglin Luo  1 ,  Yoshiaki Manse  1 ,  Saowanee Chaipech  1  2 ,  Yutana Pongpiriyadacha  3 ,  Osamu Muraoka  1 ,  Toshio Morikawa  1
Affiliations
  • 1. Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka 577-8502, Osaka, Japan.
  • 2. Faculty of Agro-Industry, Rajamangala University of Technology Srivijaya, Thungyai, Nakhon Si Thammarat 80240, Thailand.
  • 3. Faculty of Science and Technology, Rajamangala University of Technology Srivijaya, Thungyai, Nakhon Si Thammarat 80240, Thailand.
PMID: 36232534 DOI: 10.3390/ijms231911233
Abstract

With the aim of searching for phytochemicals with aromatase inhibitory activity, five new prenylcoumarins, mammeasins K (1), L (2), M (3), N (4), and O (5), were isolated from the methanolic extract of Mammea siamensis (Miq.) T. Anders. flowers (fam. Calophyllaceae), originating in Thailand. The stereostructures of 1-5 were elucidated based on their spectroscopic properties. Among the new compounds, 1 (IC50 = 7.6 µM) and 5 (9.1 µM) possessed relatively strong inhibitory activity against aromatase, which is a target of drugs already used in clinical practice for the treatment and prevention of estrogen-dependent breast Cancer. The analysis through Lineweaver-Burk plots showed that they competitively inhibit aromatase (1, Ki = 3.4 µM and 5, 2.3 µM). Additionally, the most potent coumarin constituent, mammea B/AB cyclo D (31, Ki = 0.84 µM), had a competitive inhibitory activity equivalent to that of aminoglutethimide (0.84 µM), an aromatase inhibitor used in therapeutics.

Keywords
Calophyllaceae; Lineweaver–Burk analysis; Mammea siamensis; aromatase inhibitor; mammeasin; prenylcoumarin.
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