Hong-Jin Han

Apoptosis inducement of bigelovin from Inula helianthus‐aquatica on human Leukemia U937 cells

Inula helianthus‐aquatica C. Y. Wu is a traditional medicinal plant used to treat some cancers in folk herbal medicine of Yunnan, China. Bigelovin, a sesquiterpene lactone isolated from this herb, potently inhibits the growth of a panel of eight cancer cell lines, especially in human monoblastic leukemia U937 cells with an IC50 value of 0.47 µM. Characteristic morphological features of apoptosis were observed in U937 cells treated with bigelovin. Annexin V and nuclear DNA content distribution assays showed that the percentage of Annexin V positive cells increased to 8.86% (24 h) with 1 µM bigelovin treatment, and cells treated with bigelovin at this concentration apparently arrested at G0/G1 phase compared with the control. These data suggested that cytotoxic effect of bigelovin on U937 cells involves induction of apoptosis, and the cell cycle is arrested at G0/G1 phase. Copyright

Natural Inhibitors of DNA Topoisomerase I with Cytotoxicities

DNA Topoisomerase I can cause DNA breaks and play a key role during cell proliferation and differentiation. It is an important target for anticancer agents. While screening for anticancer compounds, seven natural compounds, 1–7, showed potent cytotoxicities against a panel of ten cancer cell lines. Moreover, an inhibition assay demonstrated that they are also DNA topoisomerase I inhibitors, in which inhibitors 1–5 are new ones.

Antimicrobial, Cytotoxic Lignans and Terpenoids from the Twigs of Pseudolarix kaempferi

Seven new compounds, including four lignans, (+)-(8S,8′S)-9,9′-dibenzoylsecoisolariciresinol (1), (+)-(8S*,8′R*)-4,4′-dimethyloxomatairesinol (2), (+)-(7S*,8R*,8′R*,9′S*)-9′-n-butoxytsugacetal (3), and pseudolarkaemin A (4), a pyronane glycoside, pseudolarkaemin B (5), an ent-beyerene glycoside, pseudolarkaemin C (6), and a triterpene, 25-epi-pseudolarolide Q (7), along with 25 known compounds (8–32) were isolated from the twigs of Pseudolarix kaempferi. Their structures were elucidated mainly by the analysis of their NMR and MS data. Pseudolarolide C acid (24) was isolated for the first time as a natural product. All compounds were evaluated for antimicrobial activity against Candida albicans and Staphylococcus aureus, and cytotoxic activity against K562, HT-29, B16, BGC-823, BEL-7402, SGC-7901, U251, and A549 cancer cell lines were assayed. Results indicated that the new compounds 3, 7, and some known compounds showed antimicrobial and cytotoxic activities.

2D- and 3D-QSAR studies on 54 anti-tumor Rubiaceae-type cyclopeptides.

RA-VII, a bicyclic hexapeptide isolated from the roots of Rubia cordifolia, Rubia akane belongs to Rubiaceae-type cyclopeptides (RAs) and has attracted much attention for its potent anti-tumor activity and its bicyclic structure incorporating the isodityrosine moiety. In this work, hologram quantitative structure-activity relationship (HQSAR), comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA) methods were employed to develop 2D- and 3D-QSAR models for 54 anti-tumor RAs. The LOO cross-validated q(2) values of HQSAR, CoMFA and CoMSIA models are 0.701, 0.510 and 0.613, respectively. The predictive ability of these models was validated by the test set including 7 RAs, and the predicted IC(50) values were in good agreement with the experimental IC(50) values. HQSAR result showed that chirality descriptor plays an important role in anti-tumor activity of RAs and OMe at R(1) and R(2) is necessary for increasing their activity. CoMFA and CoMSIA results demonstrated that small bulky and electropositive side chains at R(3) position and hydrophobic groups at R(7) and R(8) positions will increase their activity, and intra-molecular hydrogen bonds between residues 1 and 4 are necessary to maintain the pharmacophoric conformation of RAs. These results may be helpful in designing novel and potential anti-tumor RAs.

Two New Norsesquiterpenes from the Fruits of Alpinia oxyphylla

Abstract Aim To investigate the constituents from the fruits of Alpinia oxyphylla Miq. Methodes Compounds were isolated and purified by various column chromatographic methods. Their structures were determined on the basis of ESI-MS and spectral analyses (including 2D NMR). Results Two sesquiterpenes, oxyphyllones E ( 1 ) and F ( 2 ) were isolated from Me 2 CO/H 2 O (70%) extract of the fruit of A. oxyphylla . Conclusion Oxyphyllones E ( 1 ) and F ( 2 ) are novel 14-norcadinene sesquiterpene and tetranorsesquiterpene, respectively.