Bioactive 2-arylbenzofuran and chalcone derivatives from Morus mesozygia Stapf

Abstract

The phytochemical investigation of the stem bark of Morus mesozygia afforded the fourteen known secondary metabolites moracin N ( 1 ), moracin S ( 2 ), mulberrofuran L ( 3 ), moracin C ( 4 ), moracin L ( 5 ), moracin M ( 6 ), moracin D ( 7 ), artopithecin A ( 8 ), isobavachalcone ( 9 ), morachalcone A ( 10 ), 2,2՛,4,4՛-tetrahydroxychalcone ( 11 ), 3 β -acetoxy-urs-12-en-11-one ( 12 ), betulinic acid ( 13 ), and 4,4′-diphenylmethane-bis(methyl) carbamates ( 14 ). Their structures were elucidated by NMR spectroscopic and mass spectrometric analyzes and their cytotoxicity (CC₅₀ for HEKa, IMR-90, and HPrEC), anti-inflammatory (TNF-α, NF-κB, and NO inhibition), antibacterial (MIC), antitumor (IC₅₀), and antiviral (CPE-based and plaque reduction assays) activities were studied. Moracin D ( 7 ) showed potent anti-inflammatory activity towards the release of NF-κB (0.57 < IC 50 < 1.21 μM). 3 β -Acetoxy-urs-12-en-11-one ( 12 ) had potent antibacterial activity towards Bacillus subtilis and Micrococcus luteus , with MIC values of 12.71 and 15.59 μM, respectively. Moracin M ( 6 ) had the highest antitumor activity (IC 50 = 19.80 μM) against SK-MEL-28 human melanoma cells. Isobavachalcone ( 9 ) exhibited activity against Human Rhinovirus 2 (HRV-2; IC 50 = 7.01 μM) with a selectivity index (SI) = 9.1 as compared to HeLa cells. None of the compounds exhibited significant antiviral activity against respiratory syncytial virus (RSV) or herpes simplex virus type 2 (HSV-2). Out of the isolated compounds, moracin D ( 7 ), isobavachalcone ( 9 ) and marsformoxide B ( 12 ), may be considered to be promising leads for the development of anti-inflammatory (NF-κB), antiviral (HRV-2), and antibacterial ( B. subtilis and M. luteus ) agents, respectively.