Jose Luis López

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.

Leishmanicidal Activity of Some Aliphatic Diamines and Amino-Alcohols

A number of aliphatic diamines and amino-alcohols and several of their alkyl, acyl and carbamoyl derivatives, have been synthesised and evaluated in vitro on cultures of Leishmania spp. In general, diamine derivatives resulted to be more potent than their amino-alcohol or amino-ether analogues. Two diamine derivatives (8b and 9d) and one amino-alcohol (6a) showed a fair inhibition of parasite growth, at concentrations below 10 microg/mL, with potencies close to that of the reference drug, amphotericin B. Some SAR considerations have been deduced.

Antifungal activity of scopoletin and its differential accumulation in Ulmus pumila and Ulmus campestris cell suspension cultures infected with Ophiostoma ulmi spores

Abstract Inoculation of cell suspension cultures derived from Ulmus pumila , a species resistant to Dutch elm disease (DED) and U. campestris , a susceptible elm, with spores of Ophiostoma ulmi , differentially induced the accumulation of the hydroxycoumarin scopoletin. This coumarin was induced rapidly and accumulated mainly in the medium of the challenged resistant culture. In in vitro bioassays, scopoletin showed a direct antifungal activity against O. ulmi spore germination being more sensitive to this inhibitory activity than mycelial growth. The significance of scopoletin in vivo is also discussed.

Lignans from Juniperus thurifera

Abstract The isolation and identification of two new natural lignans, (-)epi-podorhizol and deoxypicropodophyllotoxin, and 12 known lignans from a hexane extract of Juniperus thurifera is described.

Diarylmethyloxime and hydrazone derivatives with 5-indolyl moieties as potent inhibitors of tubulin polymerization.

We describe the synthesis and biological evaluation of a series of diarylmethyloxime and diarylmethylhydrazone analogues that contain an indole ring and different modifications on the nitrogen of the bridge. Several compounds showed potent tubulin polymerization inhibitory action as well as cytotoxic activity against cancer cell lines. The N-methyl-5-indolyl substituted analogues are more potent than ethyl substituted ones. The most potent inhibitors of tubulin polymerization are the diarylketones and the diaryloximes. The cytotoxicity against several cancer cell lines is lower for the oximes than for the ketones. Other substitutions on the imine nitrogen greatly reduce the tubulin inhibitory and/or cytotoxic potencies.

The imidazo[2,1-a]isoindole system. A new skeletal basis for antiplasmodial compounds

The in vitro antiplasmodial activity of some dihydrostilbenamides, phtalazinones, imidazo[2,1-a]isoindole and pyrimido[2,1-a]isoindole derivatives related to the natural dihydrostilbenoid isonotholaenic acid is reported. The evaluation was performed on cultures of F32 strain of Plasmodium falciparum and potent representative compounds were also evaluated in the ferriprotoporphyrin IX biomineralization inhibition test (FBIT). Compounds having the imidazo[2,1-a]isoindole skeleton were the most active and one compound of this group resulted to be as potent as chloroquine, but acting through a mechanism different that of the inhibition of heme biomineralization.

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.

Neo-clerodane diterpenoids from Croton schiedeanus

Two new neo-clerodane type furano diterpenoids were isolated from the aerial part of Croton schiedeanus, besides the clerodane diterpenes cis- and trans-dehydrocrotonin, previously isolated from other species of Croton. Structural elucidation was achieved on basis of extensive NMR experiments, including X-ray diffraction analysis and molecular mechanics calculations. The previously known flavonoids ayanin and quercetin-3,7-dimethyl ether were also obtained from the extract of this plant.

Lignans from polar extracts ofJuniperus thurifera

Abstract Three new natural lignans, methyl deoxypodophyllotoxinate, podophyllotoxinic acid and 7β-hydroxydihydrosesamin, 11 known lignans and two cinnamyl alcohols were isolated and identified from a chloroform extract of Juniperus thurifera leaves. Assignment of the 13 C NMR spectrum of β-methyl peltatin B was also performed through direct and long-range heteronuclear 2D NMR analysis, amending previous assignments.

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.