Shu Li Chen

Bioactive Cembrane Diterpenoids of Anisomeles indica

Five new cembrane-type diterpenoids with a trans-fused alpha-methylene-gamma-lactone (1-5), a new flavonoid glucoside (6), and 17 known compounds were isolated from a methanol extract of Anisomeles indica. The structures of 1-6 were elucidated by spectroscopic analysis, and the absolute configuration of compound 1 was determined using the modified Moshers method. Compound 8 (4,5-epoxovatodiolide) exhibited cytotoxicity against a small panel of human cancer cell lines. Additionally, compounds 4 and 7 (ovatodiolide) exhibited selective antiplatelet aggregation activities toward collagen, while compounds 4, 5, and 8 showed inhibitory effects on antiplatelet aggregation induced by thrombin.

Mono-tetrahydrofuran Annonaceous Acetogenins from Annona squamosa as Cytotoxic Agents and Calcium Ion Chelators

Eight new mono-tetrahydrofuran (THF)-type annonaceous acetogenins, squafosacins B, C, F, and G (1-4), squadiolins A-C (5-7), and cis-annotemoyin-1 (8), as well as eight known annonaceous acetogenins, glabranin, annotemoyins-1 and -2, bullatencin, cis-bullatencin, and uvariamicins-I, -II, and -III, were isolated from the seeds of Annona squamosa by HPLC. The structures of all new isolates were elucidated by using spectroscopic and chemical methods. Squadiolins A (5) and B (6) showed ng/mL potency against human Hep G2 hepatoma cells and significant cytotoxic activity against human MDA-MB-231 breast cancer cells. Squafosacin B (1) also exhibited significant cytotoxic activity against human Hep G2 and 3B hepatoma and MCF-7 breast cancer cells. In addition, the chelation of mono-THF acetogenins with calcium ions was investigated using isothermal titration calorimetry.

Anti-inflammatory and Cytotoxic Neoflavonoids and Benzofurans from Pterocarpus santalinus

Five new benzofurans, pterolinuses A-E (1-5), six new neoflavonoids, pterolinuses F-J (8-13), and five known compounds (6, 7, 14-16) were isolated from an extract of Pterocarpus santalinus heartwood. All new structures were elucidated by spectroscopic methods, and configurations were confirmed by CD spectral data and optical rotation values. The isolates were evaluated for anti-inflammatory and cytotoxic activities. Six compounds (1, 2, 4, 6, 7, and 15) showed significant inhibition in at least one anti-inflammatory assay. Compound 2 showed the best selective effect against superoxide anion generation in human neutrophils with, an IC50 value of 0.19 μg/mL, and was 6.2-fold more potent than the positive control LY294002. Compound 14 showed the highest cytotoxicity against Ca9-22 cancer cells, with an IC50 value of 0.46 μg/mL.

1,5-Diphenylpent-3-en-1-ynes and methyl naphthalene carboxylates from Lawsonia inermis and their anti-inflammatory activity.

Lawsonia inermis (Lythraceae) known as henna is one of the most popular and ancient plants used in cosmetics and hair dying. It is cultivated for its leaves but other parts such as seeds, flowers, stem bark and roots are also used in traditional medicine for millennia. Henna tattoo paste also proved to be beneficial for wound healing and in several skin diseases suggesting potent anti-inflammatory activity. To evaluate henna anti-inflammatory activity, 31 compounds, including three 1,5-diphenylpent-3-en-1-yne derivatives, lawsochylin A-C and three methyl naphthalene carboxylates, lawsonaphthoate A-C, were isolated from the stems and leaves of henna utilizing a bioassay-guided fractionation. The structures of the compounds were elucidated by spectroscopic data. Two compounds, lawsochylin A and lawsonaphthoate A showed potent anti-inflammatory activity by inhibition of superoxide anion generation (IC(50)=1.80 and 1.90 μg/ml) and elastase release (IC(50)=1.58 and 3.17 μg/ml) of human neutrophils in response to fMLP or cytochalasin B. Moreover, the known compounds, luteolin, apigenin, 4S-4-hydroxy-α-tetralone, and 2-butoxysuccinic acid, also showed potent inhibition of superoxide anion generation (IC(50)=0.75-1.78 μg/ml) and elastase release (IC(50)=1.62-3.61 μg/ml).

Bioactive 6S-styryllactone constituents of Polyalthia parviflora.

Parvistones A-E (1-5), five new styryllactones possessing a rare α,β-lactone moiety and a 6S configuration, were isolated from a methanolic extract of Polyalthia parviflora leaves. The structures and the absolute configuration of the isolates were elucidated using NMR spectroscopy, specific rotation, circular dichroism, and X-ray single-crystal analysis. Compounds 8, 9, 11, and 12 were isolated for the first time. The results were supported by comparing the data measured to those of 6R-styryllactones. Moreover, a plausible biogenetic pathway of the isolated compounds was proposed. The structure-activity relationship of the compounds in an in vitro anti-inflammatory assay revealed the 6S-styryllactones to be more potent than the 6R derivatives. However, the effect was opposite regarding their cytotoxic activity. In addition, 6S-styrylpyrones isolated showed more potent anti-inflammatory and cytotoxic activity when compared to the 1S-phenylpyranopyrones obtained.

Cytotoxic N-(fluorenyl-9-methoxycarbonyl) (Fmoc)-dipeptides: Structure–activity relationships and synergistic studies

The synthesis and cytotoxic evaluation of a series of Fmoc-based dipeptides are described. Among the thirty compounds, 4a, 8a, 12a, 2b, 4b, 10b, 3c, 4c and 6c showed potent activity against HepG2, Hep3B, MCF-7, MDA-MB-231, A549 and Ca9-22 human cancer cell lines. The most active compounds (10a and 10c) showed relatively good sensitivity toward HepG2 and Ca9-22 cell lines with IC50 values of 1.0 and 0.4 microM, respectively. Additionally, compound 10c was threefold more potent than doxorubicin, the positive control, against the Ca9-22 cell line. Furthermore, 10c showed a synergistic effect and increased the cytotoxicity of doxorubicin against the MDA-MB-231 cancer cell line. Therefore, 10c could be used as a new lead compound for therapeutic development.

Indiosides G-K: steroidal glycosides with cytotoxic and anti-inflammatory activities from Solanum violaceum.

Five new steroidal glycosides (1-5) and nine known compounds were isolated from Solanum violaceum. Indiosides G (1) and H (2) are spirostene saponins with an iso-type F ring, indioside I (3) is a spirostane saponin, and indiosides J (4) and K (5) are unusual furostanol saponins with a deformed F ring. These structures represent rare naturally occurring steroidal skeletons. The structures of the new compounds were elucidated using 1D and 2D spectroscopic techniques and acid hydrolysis. Compounds 2, 3, and 7-9 exhibited cytotoxic activity against six human cancer cell lines (HepG2, Hep3B, A549, Ca9-22, MDA-MB-231, and MCF-7) with IC(50) values of 1.83-8.04 μg/mL. Steroidal saponins 3, 8, and 9 showed inhibitory effects on superoxide anion generation with IC(50) values of 2.84 ± 0.18, 0.62 ± 0.03, and 1.62 ± 0.59 μg/mL, respectively. Saponins 8 and 9 also inhibited elastase release with IC(50) values of 111.05 ± 7.37 and 4.04 ± 0.51 μg/mL, respectively. Structure-activity relationship correlations of these compounds with respect to cytotoxic and anti-inflammatory effects are discussed.

Spirostanoids with 1,4-dien-3-one or 3β,7α-diol-5,6-ene moieties from Solanum violaceum

Bioassay-guided fractionation of the CHCl3 layer of Solanum violaceum areal parts methanolic extract led to the isolation of four new steroidal sapogenins, indiosides L-O (1-4), along with eight known steroids, one lignin, and a coumarin. Indioside L is a rare spirostanoid possessing a 1,4-dien-3-one moiety in ring A. Moreover, compounds 3 and 4 represent rare examples of spirostene with the 3β,7α-diol-5,6-ene moiety compared to the normal 3β,7β-diol-5,6-ene derivatives. The cytotoxic activity of the isolates (5-14) was evaluated against human hepatoma (HepG2 and Hep3B), human lung carcinoma (A549), and human breast carcinoma (MDA-MB-231 and MCF-7).

Synthesis and Biological Evaluation of Phenanthrenes as Cytotoxic Agents with Pharmacophore Modeling and ChemGPS-NP Prediction as Topo II Inhibitors

In a structure-activity relationship (SAR) study, 3-methoxy-1,4-phenanthrenequinones, calanquinone A (6a), denbinobin (6b), 5-OAc-calanquinone A (7a) and 5-OAc-denbinobin (7b), have significantly promising cytotoxicity against various human cancer cell lines (IC50 0.08–1.66 µg/mL). Moreover, we also established a superior pharmacophore model for cytotoxicity (r = 0.931) containing three hydrogen bond acceptors (HBA1, HBA2 and HBA3) and one hydrophobic feature (HYD) against MCF-7 breast cancer cell line. The pharmacophore model indicates that HBA3 is an essential feature for the oxygen atom of 5-OH in 6a–b and for the carbonyl group of 5-OCOCH3 in 7a–b, important for their cytotoxic properties. The SAR for moderately active 5a–b (5-OCH3), and highly active 6a–b and 7a–b, are also elaborated in a spatial aspect model. Further rational design and synthesis of new cytotoxic phenanthrene analogs can be implemented via this model. Additionally, employing a ChemGPS-NP based model for cytotoxicity mode of action (MOA) provides support for a preliminary classification of compounds 6a–b as topoisomerase II inhibitors.

Bioactive components from the heartwood of Pterocarpus santalinus

One new phenanthrenedione, pterolinus K (1), and one new chalcone, pterolinus L (2) were isolated from the heartwood extract of Pterocarpus santalinus. The structures were elucidated by spectroscopic methods. Both 1 and 2 showed inhibitory effect on elastase release by human neutrophils in response to fMLP with an IC(50) value of 4.24 and 0.95 μM, and compound 1 also inhibited superoxide anion generation with IC(50) value of 0.99 μM. In addition, compound 1 showed selective cytotoxicity against HepG2 with IC(50) value of 10.86 μM, while compound 2 showed a moderate cytotoxicity against KB with IC(50) values of 17.18 μM.