RESUMO
A methanol extract of the flowers of Mammea siamensis (Miq.) T. Anders. (Calophyllaceae) showed anti-proliferative activity against human prostate carcinoma LNCaP cells (IC50 = 2.0 µg/mL). Two new coumarin-related polysubstituted benzofurans, mammeasins P (1) and Q (2), and a known polysubstituted coumarin mammea B/AC cyclo F (39) were isolated from the extract along with 44 previously reported polysubstituted coumarin constituents (3-38 and 40-47). The structures of two new compounds (1 and 2) were determined based on their spectroscopic properties derived from the physicochemical evidence including NMR and MS analyses and taking the plausible generative pathway into account. Among the coumarin constituents, mammeasins A (3, IC50 = 1.2 µM) and B (4, 0.63 µM), sugangin B (18, 1.5 µM), kayeassamins E (24, 3.0 µM) and G (26, 3.5 µM), and mammeas E/BA (40, 0.88 µM), E/BB (41, 0.52 µM), and E/BC (42, 0.12 µM) showed relatively potent anti-proliferative activity.
RESUMO
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.
Assuntos
Mammea , Plantas Medicinais , Aminoglutetimida , Aromatase , Inibidores da Aromatase/farmacologia , Cumarínicos/química , Cumarínicos/farmacologia , Estrogênios/farmacologia , Mammea/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , TailândiaRESUMO
Geranylated coumarins named mammeasins G-J (1-4) were isolated from the methanol extract of the flowers of Mammea siamensis (Miq.) T. Anders. (Calophyllaceae) originating in Thailand. Their structures were established based on detailed spectroscopic analyses. The isolates, including previously reported coumarin constituents (5-28), exhibited anti-proliferative activities against human carcinoma cell lines HSC-2, HSC-4, MKN-45, and MCF-7. Mammeasin A (7, IC50 = 13.6 µM) and surangin B (15, 15.2 µM), both consisting of the geranyl group, were found to show relatively strong activities against HSC-4 cells and their mechanisms of action were found to involve apoptotic cell death.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Cumarínicos/farmacologia , Neoplasias Gastrointestinais/patologia , Mammea/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose , Carcinoma/tratamento farmacológico , Carcinoma/patologia , Linhagem Celular Tumoral , Cumarínicos/isolamento & purificação , Flores/química , Neoplasias Gastrointestinais/tratamento farmacológico , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Plantas Medicinais/química , TailândiaRESUMO
Geranylated coumarin constituents, kayeassamin I (1) and mammeasins E (2) and F (3) were newly isolated from the methanol extract of the flowers of Mammea siamensis (Calophyllaceae) originating in Thailand, along with five known isolates, such as mammea E/BC (23), deacetylmammea E/AA cyclo D (31), deacetylmammea E/BB cyclo D (32), mammea A/AA cyclo F (34), and mammea A/AC cyclo F (35). These compounds (1-3) were obtained as an inseparable mixture (ca. 1:1 ratio) of the 3â³R and 3â³S forms, respectively. Among the isolated coumarins from the extract, mammeasins E (2, 22.6 µM), A (4, 19.0 µM), and B (5, 24.0 µM), kayeassamins E (9, 33.8 µM), F (10, 15.9 µM), and G (11, 17.7 µM), surangin C (13, 5.9 µM), and mammeas A/AA (17, 19.5 µM), E/BB (22, 16.8 µM), and A/AA cyclo F (34, 23.6 µM), were found to inhibit testosterone 5α-reductase.