Ma Angeles Castro

Synthesis and antineoplastic activity of cyclolignan aldehydes.

Several aldehydes related to methyl 9-deoxy-9-oxo-alpha-apopicropodophyllate, a selective antitumour agent against the HT-29 colon carcinoma, have been prepared and evaluated for their cytotoxic activities on four neoplastic cell lines (P-388, A-549, HT-29 and MEL-28). All of them lacked the lactone ring but maintained their cytotoxicity at, or under, the microM level.

Selective cytotoxic cyclolignans

Abstract Several derivatives of podophyllotoxin, lacking the lactone moiety and with nitrogen substituents at C-7 or C-9, have been prepared. They have been evaluated for their cytotoxic activity in P-388, A-549, HT-29 and MEL-28 culture cells. Some of them show a highly selective cytotoxicity towards HT-29 human colon carcinoma.

Synthesis and bioactivity of new antineoplastic terpenylquinones

Abstract Several monoterpenylquinones have been prepared and evaluated for their cytotoxic activity against four cell lines cultures. The size of the quinone fragment is important for the activity, being the naphtalene derivatives the most potent compounds tested. The presence of substituents on the quinone ring decreases the potency but increases the selectivity.

Cytotoxic–antineoplastic activity of hydroquinone derivatives

Several myrcenylhydroquinone derivatives have been evaluated for their cytotoxic activity against three neoplastic cell line cultures and compared with the activity previously observed on other neoplastic systems. Also a new series of this type of compounds has been prepared and the compounds synthesised have been evaluated by their GI(50) values.

Bioactive isoxazoline and oxime derivatives from 7-ketolignans

Abstract A new type of cyclolignans with an isoxazoline ring fused to the cyclolignan core has been prepared from 7-ketolignanolides by reaction with hydroxylamine. The corresponding 7-oxime derivatives have also been obtained. The compounds prepared have been evaluated for their cytotoxic activities over four cell lines.

New antineoplastic prenylhydroquinones. Synthesis and evaluation.

Several prenylhydroquinones have been prepared through Diels-Alder condensation, further functionalized or degraded chemically and then evaluated for their cytotoxic activity against some neoplastic cultured cell lines. A number of them have shown IC50 values under the microM level.

Lignopurines: A new family of hybrids between cyclolignans and purines. Synthesis and biological evaluation

A new family of hybrids between cyclolignans related to podophyllic aldehyde, a non-lactonic cyclolignan, and purines were prepared and evaluated against several human tumour cell lines. Both fragments, cyclolignan and purine, were linked through aliphatic and aromatic chains. The influence on the cytotoxicity of the purine substitution and the nature of the linker is analyzed. The new family was slightly less cytotoxic than the parent podophyllic aldehyde, although the selectivity is maintained or even improved and among the linkers used, the presence of an aromatic ring gave the most potent and selective derivatives within the new series tested. Cell cycle and confocal studies demonstrate that these derivatives interfere with the tubulin polymerization and arrest cells at the G(2)/M phase, in the same way than the parent compounds podophyllotoxin and podophyllic aldehyde do.

2,3-FUNCTIONALLY DIALKYL-1,4-BENZOHYDROQUINONE DIACETATE DERIVATIVES FROM CLEAVAGE OF EPOXIDES

Se han preparado una serie de nuevos compuestos del tipo diacetatos de 1,4-benzohidroquinona-2,3-dialquilsustituidos, por oxidacion degradativa de epoxidos III, obtenidos del producto de condensacion Diels-Alder entre el monoterpeno mirceno y la 1,4-benzoquinona. La naturaleza de los productos aislados depende de los grupos funcionales presentes en las cadenas alquilicas

New 1,4-anthracenedione derivatives with fused heterocyclic rings: synthesis and biological evaluation

Several terpenylquinones derived from 1,4-anthracenedione (1,4-anthracenequinone, AQ) have been prepared by addition or substitution nucleophilic reactions and further transformed into extended polycyclic systems, which mainly kept the 1,4-quinone moiety fused to different nitrogen-heterocyclic rings (pyrrole, imidazole, pyrazine or quinoxaline) into the structure. The compounds synthesized were evaluated for their antineoplastic, antifungal and antiviral activities. GI50 antineoplastic values remained under μM levels for AQs, while the heterocyclic derivatives showed antifungal MIC values in the low μg mL−1 range against yeasts and filamentous fungi. Only few compounds displayed a discrete non-selective antiherpetic activity in the μg mL−1 range.

New Hybrids Derived from Podophyllic Aldehyde and Diterpenylhydroquinones with Selectivity toward Osteosarcoma Cells

A new family of molecular hybrids, between cyclolignans related to podophyllic aldehyde and several diterpenylnaphthohydroquinones (DNHQ), was prepared and its biological activity evaluated in several human solid tumor cell lines, which are representative of the most prevalent solid tumors in the Western world. Both cyclolignan and quinone fragments were linked through aliphatic or aromatic spacers. The new hybrid family was evaluated for its cytotoxicity, and it was found that the hybrids were several times more potent against the osteosarcoma cell line MG-63 than against MCF-7 and HT-29 cell lines. The presence of an aromatic ring in the linker gave the most potent and selective agent, improving the cytotoxicity of the parent compounds. Cell cycle studies demonstrated that this hybrid induces a strong and rapid apoptotic effect and arrests cells at the G2/M phase of the cell cycle, in the same way that the parent compound podophyllic aldehyde does.