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• In-vitro anti-amoebic activity of Myristica cinnamomea King fruit extract and its purified Malabaricones (A-C). • Malabaricone C showed potent activity against A. castellanii with an IC 50 of 49.95 µM. • Malabaricones (A-C) induced necrotic cell death in trophozoites. • Malabaricones B and C are possible alternative therapeutic options against A. castellanii infections. Acanthamoeba castellanii is an opportunistic free-living amoeba (FLA) pathogen which can cause fatal central nervous system (CNS) infection, granulomatous amoebic encephalitis (GAE) and potentially blinding ocular infection, Acanthamoeba keratitis (AK). Acanthamoeba species remain a challenging protist to treat due to the unavailability of safe and effective therapeutic drugs and their ability to protect themselves in the cyst stage. Natural products and their secondary metabolites play a pivotal role in drug discovery against various pathogenic microorganisms. In the present study, the ethyl acetate extract of Myristica cinnamomea King fruit was evaluated against A. castellanii (ATCC 50492), showing an IC 50 of 45.102 ± 4.62 µg/mL. Previously, the bio-guided fractionation of the extract resulted in the identification of three active compounds, namely Malabaricones (A-C). The isolated and thoroughly characterized acylphenols were evaluated for their anti-amoebic activity against A. castellanii for the first time. Among tested compounds, Malabaricone B (IC 50 of 101.31 ± 17.41 µM) and Malabaricone C (IC 50 of 49.95 ± 6.33 µM) showed potent anti-amoebic activity against A. castellanii trophozoites and reduced their viability up-to 75 and 80 %, respectively. Moreover, both extract and Malabaricones also significantly (p < 0.05) inhibit the encystation and excystation of A. castellanii , while showed minimal toxicity against human keratinocyte cells (HaCaT cells) at lower tested concentrations. Following that, the explanation of the possible mechanism of action of purified compounds were assessed by detection of the state of chromatin. Hoechst/PI 33342 double staining showed that necrotic cell death occurred in A. castellanii trophozoites after 8 h treatment of Malabaricones (A-C). These findings demonstrate that Malabaricones B and C could serve as promising therapeutic options against A. castellanii infections. [ABSTRACT FROM AUTHOR]

A new acylphenol, malabaricone E ( 1 ) together with the known malabaricones A-C ( 2 – 4 ), maingayones A and B ( 5 and 6 ) and maingayic acid B ( 7 ) were isolated from the ethyl acetate extract of the fruits of Myristica cinnamomea King. Their structures were determined by 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Compounds 3 (1.84 ± 0.19 and 1.76 ± 0.21 μM, respectively) and 4 (1.94 ± 0.27 and 2.80 ± 0.49 μM, respectively) were identified as dual inhibitors, with almost equal acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibiting potentials. The Lineweaver–Burk plots of compounds 3 and 4 indicated that they were mixed-mode inhibitors. Based on the molecular docking studies, compounds 3 and 4 interacted with the peripheral anionic site (PAS), the catalytic triad and the oxyanion hole of the AChE. As for the BChE, while compound 3 interacted with the PAS, the catalytic triad and the oxyanion hole, compound 4 only interacted with the catalytic triad and the oxyanion hole. [ABSTRACT FROM AUTHOR]

A dimeric acylphenol and a potent α-glucosidase inhibitor, giganteone D (IC 50 5.05 μM), was isolated and characterized from the bark of Myristica cinnamomea King. The bark also yielded an acylphenol with an unprecedented skeleton for which the name cinnamomeone A (IC 50 358.80 μM) was proposed. Their structures were established by means of NMR and MS spectrometric analyses. The Lineweaver–Burk plot of giganteone D indicated that it was a mixed-type inhibitor. This is the first report on the α-glucosidase inhibiting potential of acylphenols. [ABSTRACT FROM AUTHOR]