Bioactive 2-arylbenzofuran and chalcone derivatives from Morus mesozygia Stapf

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), 3β-acetoxy-urs-12-en-11-one (12), betulinic acid (13), and 4,4'-diphenylmethane-bis(methyl) carbamate (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 < IC₅₀ < 1.21 μM). 3β-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 (IC₅₀ = 19.80 μM) against SK-MEL-28 human melanoma cells. Isobavachalcone (9) exhibited activity against Human Rhinovirus 2 (HRV-2; IC₅₀ = 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.