Esther Caballero

Synthesis and pharmacological activity of diarylindole derivatives. Cytotoxic agents based on combretastatins

Taking into account the structure of Combretastatins, we have synthesized and assayed for cytotoxic activity of new indole derivatives. Two aryl groups are maintained in the cis orientation required for activity by means of an indole moiety built up on less active ketoderivatives used as starting materials.

Design, synthesis and cytotoxic activities of naphthyl analogues of combretastatin A-4.

The 3,4,5-trimethoxyphenyl and 3-hydroxy-4-methoxyphenyl rings of combretastatin A-4 are deemed optimal for its activity as antimitotic agent. The replacement of either one by a naphthalene ring results in compounds with a potency comparable to that of the parent compound. These results show that the naphthalene ring is a good surrogate for the 3,4,5-trimethoxyphenyl or the 3-hydroxy-4-methoxyphenyl rings of combretastatin A-4 and that neither of them is essential for the antitumor activity.

Synthesis and cytotoxic activity of different open indolocarbazole alkaloid analogues.

An array of 4-(aryl or indolyl)pyrrolo[3,4-c]carbazole-1,3-diones (open analogues of indolocarbazole alkaloids), 10-(aryl or indolyl)pyrrolo[3,4-b]carbazole-1,3-diones, and different derivatives have been prepared using a Diels-Alder plus Fischer indolization approach and tested as cytotoxic agents. Some representative compounds display interesting cytotoxic profiles.

A NEW APPROACH TO THE SYNTHESIS OF PODOPHYLLOTOXIN BASED ON EPIMERIZATION REACTIONS

A formal synthesis of podophyllotoxin has been achieved by means of the well known conjugate addition-alkylation of 5H-furan-2-one, followed by cyclization and controlled epimerizations. This approach represents a useful new route to the 8,7′-trans-stereochemistry of aryltetralin lactones, that in other methodologies requires the opening and reclosure of the lacton ring.

Diterpene acids from Juniperus communis subsp. Hemisphaerica

Abstract Thirteen diterpenoids with labdane and pimarane skeletons have been identified in the acid fraction of a hexane extract from leaves of Juniperus communis subsp. hemisphaerica . Among these, 15- O -palmitoyl isocupressic acid has been isolated for the first time from a natural source.

Components from Santolina rosmarinifolia, subspecies rosmarinifolia and canescens

Abstract Apart from other already known components, two-eudesmane-type alcohols, two coumarins and a new spiroketalenolether-type acetylene were isolated from S. rosmarinifolia , subspp. rosmarinifolia and canescens . The structures assigned were based on their spectral properties. The relative stereochemistries of the new acetylene at C-11 and that of the known spiranic acetylenes were assigned by NMR-NOE experiments.

Heterolignanolides. Furo- and thieno-analogues of podophyllotoxin and thuriferic acid

Abstract The conjugate addition–alkylation to 5H-furan-2-one followed by cyclization and controlled epimerizations have been applied to the synthesis of new furo- and thieno-lignan analogues. Podophyllotoxin and thuriferic acid heteroanalogues have been obtained by this methodology, as representative members of these families.

Leishmanicidal activity of combretastatin analogues and heteroanalogues.

We have investigated the in vitro leishmanicidal activity of representative members from series II-V of combretastatin analogues and heteroanalogues. Most of them exhibited different degrees of activity against various strains of Leishmania spp. The diaryl(heteroaryl)ethane system or the more complex fused heterocyclic stilbenoids, constitute useful skeletal bases to support some kind of antiparasitic activity. Particularly, the incorporation of 2-furyl substituents led to potent antileishmanial compounds, which have been selected for in vivo testing on murine models.

Antihypertensive effect of some oxazolo[3,2-a]pyridines, thiazolo[3,2-a]pyridines and pyrido[2,1-b]oxazines in conscious spontaneously hypertensive rats

The antihypertensive activity of eighteen oxazolo[3,2‐a]pyridine, fhiazolo[3,2‐a]pyridine and pyrido[2,1‐b]oxazine derivatives has been evaluated in conscious spontaneously hypertensive rats (SHRs), and compared with that of nifedipine, used as reference.

Synthesis and pharmacological activities of some pyrido[2,1-b]oxazines

Abstract A novel kind of fused heterocyclic compounds, with the pyrido[2,1- b ]oxazine ring have been prepared and tested for their pharmacologic properties. Some of them have shown long-term antihypertensive-bradycardic effects as well as anti-inflammatory, spasmolytic and other effects.