Two new chromanone acids from the stem bark of Calophyllum peekelii Lauterb

Abstract Three chromanone acids were isolated from the stem bark of Calophyllum peekelii Lauterb. Among them are two new chromanone acids, calopeekelioic acids A (1) and B (2), along with calolongic acid (3), Their structures were established by analyzing a combination of HRESIMS, 1 D, and 2 D NMR spectra. Chromanone acids 1-3 were evaluated for their antiplasmodial activity against Plasmodium falciparum strain 3D7. Compounds 1-2 showed high activity with an IC50 value of 1.70 and 1.01 µg/mL, respectively. Graphical abstract


Introduction
Calophyllum genus (Calophyllaceae), a large group of rainforest tropical of Southeast Asia, comprises approximately 165 species (Stevens 1980;Tanjung et al. 2018). Investigations of the Calophyllum plant reported xanthones (Ismail et al. 2015;Tanjung et al. 2021) and chromanone acids (Cottiglia et al. 2004;Lim et al. 2015). The phenolic compounds of Calophyllum display activities such as an anti-corona virus (Shen et al. 2005), anticancer Tanjung et al. 2022), and antimalarial (Hay et al. 2004) properties. C. peekelii, locally known as Nyamplung, are endemic plant species in Papua Island, Indonesia. Three chromanone acids, including two new compounds, calopeekelioic acids A (1) and B (2), were isolated from the stem bark of C. peekelii. The structures of three chromanone acids (1-3) were identified by spectroscopic analysis and compared by reported spectral data. According to Trager and Jensen's methods, isolates (1-3) were also assayed for antiplasmodial activity against P. falciparum strain 3D7.

Plant material
The C. peekelii came from Werekopa Village, District Fakfak, Papua Province, Indonesia, in Jun 2019, and a senior botanist identified the plant specimen (CP 20191406) at Herbarium Bogoriense LIPI, Indonesia.

Extraction and isolation
The chromanone acids extracted in the air-dried stem bark of C. peekelii (2.7 kg) with MeOH were carried out for one week to get MeOH extract (200 g). The MeOH extract was extracted with hexane and EtOAc by partition method to get hexane extract (15 g) and EtOAc extract (5.2 g). The fractionation of EtOAc extracts using a gravity column with the mobile phase hexane: ethyl acetate (4: 1 to 1: 1) produces fractions A, and B. Fraction A (3 g) was separated from CC using a stationary phase Sephadex LH-20 and methanol as the mobile phase to produce subfractions A 1 and A 2 . Purification of subfraction A 1 by radial planar chromatography using a mixture of hexane and acetone 2.5% produced calopeekelioic acid A (1, 6.3 mg), B (2, 8.0 mg), and calolongic acid (3, 21.0 mg).

Antiplasmodial assay
All compounds 1-3 were evaluated for their antiplasmodial activity against P. falciparum strain 3D7 using Trager and Jensen's methods (Hay et al. 2004;Tanjung et al. 2016). The reference substance is the control positive using chloroquine.

Conclusions
Calopeekelioic acids A (1) and B (2), two new chromanone acids, were isolated from the stem bark of C. peekelii and showed high activity against P. falciparum.