Baoliang Cui

Novel cytotoxic 1H-cyclopenta[b]benzofuran lignans from Aglaia elliptica

Abstract Bioassay-guided fractionation of the stems and fruits of Aglaia elliptica using human oral epidermoid carcinoma (KB) cells, led to the isolation of five cyclopenta[b]benzofurans, constituted by methyl rocaglate (1) and four novel compounds (2–5), along with three known dammarane triterpenoids. Compound 5 possesses an unusual formyl ester substituent at the C-1 position. The structures of the novel compounds were established on the basis of spectroscopic methods. Compounds 1–5 were found to be very potent cytotoxic substances when evaluated against a panel of human cancer cell lines.

Modulation of the Multidrug-Resistance Phenotype by New Tropane Alkaloid Aromatic Esters from Erythroxylum pervillei

Nine tropane alkaloid aromatic esters (1-9) were isolated from the roots of Erythroxylum pervillei by following their potential to reverse multidrug-resistance with vinblastine-resistant oral epidermoid carcinoma (KB-V1) cells. All isolates, including seven new structures (3-9), were evaluated against a panel of human cancer cell lines, and it was found that alkaloids 3 and 5-9 showed the greatest activity with KB-V1 cells assessed in the presence of vinblastine, suggesting that these new compounds are potent modulators of P-glycoprotein. Confirmatory results were obtained with human ovarian adenocarcinoma (SKVLB) cells evaluated in the presence of adriamycin and synergistic studies performed with several cell lines from the NCI tumor panel. The structures of the new compounds were determined using spectroscopic techniques. Single-crystal X-ray analysis was performed on the monoester, tropane-3 alpha,6 beta,7 beta-triol 3-phenylacetate (1).

Pervilleines B and C, new tropane alkaloid aromatic esters that reverse the multidrug-resistance in the hollow fiber assay

P-Glycoprotein (Pgp)-mediated drug efflux can yield a multidrug-resistance phenotype that is associated with poor response to cancer chemotherapy. Pervilleines B and C (PB and PC), two new tropane alkaloid aromatic esters obtained from a chloroform extract of the roots of Erythroxylum pervillei as the result of bioactivity-guided fractionation, were found to restore the vinblastine (VLB) sensitivity of cultured multidrug-resistant KB-V1 cells, with 50% inhibitory concentration values of 0.17 microM in each case. To explore the potential relevance of this response, KB-V1 cells were placed in hollow fibers and implanted into NCr nu/nu mice. Cell growth was not significantly inhibited when VLB or PB or PC were administered as single agents, but when used in combination with vinblastine inhibition of up to 77.7% was observed. Equimolar doses of verapamil were less effective. These data suggest that PB and PC are effective inhibitors of Pgp and should be further evaluated for clinical utility.

NOVEL CYTOTOXIC RING-A SECO-CYCLOARTANE TRITERPENES FROM GARDENIA CORONARIA AND G. SOOTEPENSIS

Abstract Coronalolide methyl ester (1), coronalolide (2), and coronalolic acid (3) were isolated from the leaves and/or stems of Gardenia coronaria. A further compound, methyl coronalolate acetate (4), was purified from the stems after methylation. The novel compounds 1–4 have the rare ring-A seco-cycloartane carbon skeleton and their structures were assigned on the basis of spectral data and molecular modeling, as well as X-ray crystallography performed on 1. Compounds 1 and 2 were also isolated from the leaves of Gardenia sootepensis and showed broad cytotoxic activity when evaluated against a panel of human cancer cell lines.

Limonoids from Azadirachta excelsa

Activity-directed fractionation of a stem extract of Azadirachta excelsa using KB (human oral epidermoid carcinoma) cells led to the isolation of four meliacin-type limonoids. Two of these constituents were novel, namely, 2,3-dihydronimbolide and 3-deoxymethylnimbidate, and these were purified along with the known compounds, nimbolide and 28-deoxonimbolide. The structures of the new compounds were determined by spectroscopic methods. Nimbolide and 28-deoxonimbolide were broadly cytotoxic when evaluated against a panel of human cancer cell lines, while the two novel compounds were inactive in this regard. The defection of nimbolide and 28-deoxonimbolide as cytotoxic constituents was facilitated by an electrospray LC/MS dereplication procedure.

Quinoline alkaloids from Acronychia laurifolia.

Bioassay-directed fractionation of a root extract of Acronychia laurifolia (Rutaceae) using the KB-V1+ human tumor cell line led to the isolation of six quinoline alkaloids. One of these alkaloids is novel, namely, 2,3-methylenedioxy-4,7-dimethoxyquinoline and the other five were identified as the known compounds, evolitrine, gamma-fagarine, skimmianine, kokusaginine and maculosidine. Two known bis-tetrahydrofuran lignans, sesamolin and yangambin, were also identified. The structure of the new alkaloid was determined by spectroscopic methods. All of the isolates were evaluated against a panel of human cancer cell lines; four of the alkaloids showed weak cytotoxic activity.

The dereplication of plant-derived natural products

Publisher Summary The dereplication of natural products is gaining greater importance in optimizing the process of natural product drug discovery as the pace of evaluating natural product extracts for their biological potential has increased. Over the years, as new technologies are introduced into analytical chemistry, they have been applied to detect known compounds before isolation and structure elucidation is initiated. Initially, chromogenic reagents were used to obtain information on the chemical classes of compounds found in natural product extracts. Though not very powerful in predictive nature as to the identity of compounds present, chemical class information was used in order to prioritize natural product extracts for subsequent isolation. The power of partially separating extracts with paper and thin-layer chromatographic techniques before subsequently spraying with chromogenic reagents, increased the ability of researchers to distinguish different classes of compounds from one another. TLC techniques were of major importance to many natural product drug discovery groups and are still widely used today. One of the most critical technologies to become available in the past decade and to advance the prioritization process is that of the computer. With the advent of small and powerful computers, information that is widely distributed and difficult to search, is now readily searchable by using any desired parameter such chemical, taxonomic, or pharmacological.