Jaime Bermejo

Two sesquiterpene lactones from Centaurea canariensis

Abstract From the aerial part of Centaurea canariensis three sesquiterpene lactones were isolated: cynaropicrin, deacylcynaropicrin and aguerin A . The same species, grown from seed, yielded cynaropicrin, deacylcynaropicrin and aguerin B . The guaianolides aguerin A and B are reported for the first time. Aguerin B was subsequently found to be present in Centaureana linifolia, C. canariensis (var subspinnata ) and C. sventenii .

Antiproliferative Activity of Abietane Diterpenoids against Human Tumor Cells

In the present study, the cytotoxicity of 30 diterpenoids with an abietane or a halimane skeleton was determined against five human tumor cell lines (HL-60, U937, Molt-3, SK-MEL-1, and MCF-7). Diterpenoids containing an abietane skeleton including taxodone (1) and taxodione (2), as well as the semisynthetic derivatives 12, 14, 15, 17, and 22, were the most cytotoxic compounds for human leukemia cells. Overexpression of the protective mitochondrial proteins Bcl-2 and Bcl-x(L) did not confer resistance to abietane diterpene-induced cytotoxicity. Studies performed on HL-60 cells indicated that growth inhibition triggered by compounds 1, 12, 14, and 15 was caused by induction of apoptosis. This was prevented by the nonspecific caspase inhibitor Z-VAD-FMK and, in the case of compounds 14 and 15, reduced by the selective caspase-8 inhibitor Z-IETD-FMK. Cell death induced by these abietane diterpenes was found to be associated with the release of mitochondrial proteins, including cytochrome c, Smac/DIABLO, and AIF (apoptosis-inducing factor), accompanied by dissipation of the mitochondrial membrane potential (ΔΨ), and modulated by inhibition of extracellular signal-regulated kinases signaling and the p38 mitogen-activated protein kinase pathway.

Bioactive humulene derivatives from Asteriscus vogelii

The bioactive fractions obtained from the extract of Asteriscus vogelii afforded a new humulene derivative, the 8-oxo-6,7,9,10-tetrahydrohumulen-1,12-olide (1), in addition to the known asteriscunolides A (2), C (3) and D (4), and the acids 8-oxo-alpha-humula-6Z,9Z-dien-12-oic acid (5), 8-oxo-alpha-humula-6E,9Z-dien- 12-oic acid (6) and 8-oxo-alpha-humula-6E,9E-dien-12-oic acid (7), characterized as their methyl esters. Evaluation of their phytotoxic and cytotoxic activities was accomplished. Compounds 3 and 4 gave the highest inhibition of plant cell cultures and of the plant Lemna paucicostata. Compound 4 was also the most active against P-338 lymphoma in mice, A-549 carcinoma of human lung, HT-29 carcinoma of human colon and MEL-28 human melanoma.

Flavonoids from Artemisia campestris subsp. marítima

Abstract Five flavonoids and an acetophenone derivative were isolated from Artemisia campestris subsp. maritima , including a new flavanone, 5,8,4′-trihydroxyflavanone, and 5,6-dihydroxy-4′-methoxyflavanone, obtained for the first time from a natural source. The known natural products were 5,4′-dihydroxy-7,3′-dimethoxyflavanone,7,3′-dimethoxy-3,5,4′-trihydroxyflavanone, 5,4′-dihydroxy-6,7-dimethoxyflavone and 3-(isopent-2-enyl)-4-hydroxy-acetophenone.

Anticancer activity of novel hybrid molecules containing 5-benzylidene thiazolidine-2,4-dione.

Hybridization of two different bioactive molecules with different mechanism of action is one of the methods that are being adopted to treat cancer. Molecules bearing a thiazolidine-2,4-dione scaffold have been recognized as antineoplastic agents with a broad spectrum of activity against many cancer cell lines. In this manuscript we have described the synthesis and biological evaluation of two series of N-3-substituted-5-arylidene thiazolidine-2,4-diones, bearing the α-bromoacryloylamido moiety at the para- or meta-position on the phenyl of the arylidene portion. We have observed that selected compounds 5a, 5c and 5g suppress proliferation of human myeloid leukaemia HL-60 and U937 cells by triggering morphological changes and internucleosomal DNA fragmentation, which are well-known features of apoptosis. Finally, our results indicated that the investigated compounds induced apoptotic cell death through a mechanism that involved activation of multiple caspases and was also associated with the release of cytochrome c from the mitochondria.

Chlorohyssopifolin C, D, E and vahlenin, four new sesquiterpene lactones from Centaurea hyssopifolia☆

Abstract On the basis of chemical and spectroscopic evidence, structures are assigned to four new sesquiterpene lactones: chlorohyssopifolin C, D and E (guaiano

A facile chemoselective deacetylation in the presence of benzoyl and p-bromobenzoyl groups using p-toluenesulfonic acid

Abstract The acetyl group was chemoselectively cleaved in the presence of p -toluenesulfonic acid ( p -TsOH) in CH 2 Cl 2 /MeOH without affecting the benzoyl (benzoate and p -bromobenzoate) groups and no transesterification product was observed. The treatment of protected carbohydrates with p -TsOH·H 2 O at room temperature usually required a longer reaction time than at 40°C. Other types of sulfonic acid such as 10-camphorsulfonic (CSA) led to similar results.

The structure and stereochemistry of artemin

Abstract Artemin was isolated from the aerial part of Artemisia maritima . Its structure and stereochemistry were determined on the basis of chemical transformations and spectral evidence

Hypochaerin: a new sesquiterpene lactone from Hypochaeris setosus

Abstract Hypochaeris setosus contains desacetoxymatricarin, achillin, 1-hydroxy-6β,7α,11β-H-eudesm-4-en-6,12 olide, jacquinelin and hypochaerin, a new guaianolide, established as 3-oxo-4β,5α,6β,7α,11β-H-guai-1(2)-en-6,12 olide.

New insights into the structure-cytotoxicity relationship of spirostan saponins and related glycosides.

A variety of spirostan saponins and related glycosides were synthesized and evaluated for their cytotoxicity against the human myeloid leukemia cell line (HL-60). A linear glycosylation strategy allowed for accessing a variety of functionalization patterns at both the spirostanic and the saccharide moieties, which provides new information regarding the structure-cytotoxicity relationship of this family of steroidal glycosides. Intriguing results were achieved with respect to hecogenyl and 5α-hydroxy-laxogenyl β-chacotriosides, turning out to be the former very cytotoxic and the latter no cytotoxic at all. Importantly, the partially pivaloylated β-d-glucosides of 5α-hydroxy-laxogenin were the most potent cytotoxic compounds among all tested glycosides. This comprises the first report on acylated spirostanyl glucosides displaying significant cytotoxicity, and therefore, it opens up new opportunities toward the development of saponin analogues as anticancer agents.