Studies On The Bioactive Constituents Of Two Moraceous Medicinal Plants

Artocarpus and Cudrania are two important genera of Moraceous plants. Somespecies of Artocarpus have been used as traditional folk medicines in Indonesia, Thailand,Taiwan, and Sri Lanka to treat live cirrhosis, hypertension, backache, rheumatism, malarial,fever, dysentery, and tuberculosis. They also were reported to possess anti-inflammatoryand detoxifying effects and control of blood sugar levels in diabetic patients. Most speciesof Cudrania are Chinese folk medicines to cure hepatitis, rheumatism, bruising, jaundice,scabies, dysmenorrhea, external and internal hemorrhage, and chronic gastritis. The extractfrom the root barks of Cudrania tricuspidata are applied in clinic for the treatment ofdigestive apparatus tumor, especially gastric carcinoma. Previously, a large number ofprenylated flavonoids and xanthones were isolated from Artocarpus and Cudrania species,some of which were found to exhibit cytotoxic and antiplatelet activities, inhibitoryactivities against arachidonate 5-lipoxygenase, cyclooxygenase, tyrosinase, cathepsin K,and 5α-reductase, and effects of anti-inflammatory, antimalarial, antibacterial, antilipidoxidation, and liver protection. In our continuing research on cytotoxic phenoliccompounds with isoprenoid groups from Moraceous plants, we investigated theconstituents of Artocarpus chama Buch.-Ham and Cudrania fruticosa (Roxb) Wight exKurz, which have not been studied with respect to their chemical constituents. Our primarybioassay showed that the chloroform-soluble fraction from an ethanol extract of the rootsof Artocarpus chama exhibited cytotoxic activity against human lung carcinoma (A549)and breast adenocarcinoma (MCF-7) in vitro, and the chloroform-soluble fraction from anaqueous acetone extract of the roots of Cudrania fruticosa exhibited cytotoxic activityagainst human gastric carcinoma cell lines (SGC-7901 and BGC-823) in vitro. Therefore,in order to elucidate the bioactive constituents of the two medicinal plants and search forcytotoxic agents, the studies on the constituents and bioassay of cytotoxic, anti-HIV, andantifungal activities were carried out. 1. Five new isoprenylated flavones, artochamins A?E (I-1? I-5), were isolated fromthe roots of Artocarpus chama, together with eight known comounds, artocarpin (I-6), v两种桑科药用植物生物活性成分的研究cycloartocarpin A (I-7), cudraflavone A (I-8), artonin A (I-9), artonin U (I-10),cycloartobiloxanthone (I-11), artonin E (I-12), and 3′,4′,5,7-tetrahydroxy-8-(methylbut-2-enyl)flavone (I-13). Their structures were elucidated by spectroscopic methods. Compounds I-3, I-6, I-7, I-9, I-11, and I-12 were screened for cytotoxicity against apanel of human tumor cell lines. Artonin E (I-12) showed strong cytotoxicity against 1A9(ovarian, ED50 < 1.25 μg/mL), significant activity against MCF-7 (breast adenocarcinoma,ED50 = 2.2 μg/mL), and moderate activity against HCT-8 (ileocecal, ED50 = 3.3 μg/mL)and MDA-MB-231 (breast adenocarcinoma, ED50 = 3.0 μg/mL) tumor cell lines.Artochamin C (I-3) was more potent against MCF-7, 1A9, HCT-8, and SK-MEL-2(melanoma) (ED50 = 2.0?2.3 μg/mL) than A549 (lung carcinoma), KB (epidermoidcarcinoma of the nasopharynx) and its drug-resistant (KB-VIN) variant (ED50 = 3.0?3.4μg/mL). Artocarpin (I-6) displayed weak but relatively broad inhibitory effects (ED50 =3.2?3.8 μg/mL) compared with I-3 and I-12. Compounds except for I-8 and I-10 were tested for anti-HIV activity. Compound I-13exhibited activity with EC50 and TI values of 2.24 μg/mLand 7.47, respectively. 2. Four new stilbenes with two isoprenoid groups, artostilbenes A?D (II-1? II-4), andfour mono-isoprenylated phenols with novel skeleton, artophenols A?D (II-5? II-8), wereisolated from the barks of Artocarpus chama. Their structures were elucidated on the basisof their spectral properties and X-ray crystallographic analysis. Artostilbene D (II-4) is...