Pablo A. García

Occurrence, Biological Activities and Synthesis of Kaurane Diterpenes and their Glycosides

This paper presents a review on kaurane diterpenes and their glycoside derivatives, covering aspects of their occurrence, biological activities and the synthesis of these natural products and their analogues. First, it shows and classifies diterpenes, in accordance with the already established structural criteria in the literature. Then, kaurane diterpenes are presented, focusing on their chemical structures, occurrence in the plant kingdom and their main, recently described, biological activities. Moreover, the most significant works, published between 1964 and November 2006, which describe the total synthesis or structural transformations of some kaurane diterpenes, including either semisynthetic and/or microbiological methodologies, are consisely reviewed. At this point, some general considerations on glycosides are introduced, and kaurane glycosides are presented and discussed on the basis of their toxic importance and occurrence in the plant kingdom, having focused on related aspects of their biological activities and the relationships between these activities and the structural factors of their molecules. Finally, the principal methods of glycosidation by enzymatic and chemical processes are both presented, and a few papers on the synthesis of kaurane glycosides are succinctly discussed.

Preparation and cytotoxicity of podophyllotoxin derivatives lacking the lactone ring

Abstract Several cyclolignans lacking of the lactone moiety can easily be prepared from naturally occurring lignans such as podophyllotoxin and deoxypodophyllotoxin by simple chemical transformations. Their cytotoxicity has been studied in four tumoral cell lines. Most of the compounds show similar effects in all the neoplastic systems tested, except the aldehyde 9 (methyl 9-deoxy-9-oxo-α-apopicropodophyllate) and the hydrazones 16 and 17 which show a highly selective cytotoxicity towards HT-29 human colon carcinoma. Additionally, several molecular modeling studies have been done with aldehyde 9 and the corresponding saturated aldehyde 13 in comparison with podophyllotoxin.

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.

Chemoinduction of cytotoxic selectivity in Podophyllotoxin-related lignans

Lignans are widely distributed in the plant kingdom, and display a variety of biological activities which have attracted the attention of the scientific community for decades. Several representative compounds of the cyclolignan class, such as podophyllotoxin and its semisynthetic derivative, etoposide, are currently used for the clinical treatment of warts and malign neoplasms. Other cyclolignans are involved in antineoplastic and antiarthritic clinical trials. Numerous podophyllotoxin-related compounds have been prepared through modification of nearly all the positions on the cyclolignan skeleton in the search of new, more selective and less toxic anticancer drugs. Our group has been interested in the chemoinduction of drug selectivity for several years, and we have designed and prepared new podophyllotoxin derivatives by modification mainly on the C and D-rings of the podophyllotoxin skeleton. Those derivatives, bearing an electrophilic functionality at C-9, have shown, both in vitro and in vivo, a high degree of selectivity against colon carcinoma, and less cytotoxicity for other neoplastic systems and normal kidney fibroblasts. The main structural modifications found in the literature for the podophyllotoxin skeleton in the past decade, including those from our research group, are presented in this article.

Synthesis, cytotoxicity and antiplasmodial activity of novel ent-kaurane derivatives

This paper reports on the syntheses and spectrometric characterisation of eleven novel ent-kaurane diterpenoids, including a complete set of (1)H, (13)C NMR and crystallographic data for two novel ent-kaurane diepoxides. Moreover, the antineoplastic cytotoxicity for kaurenoic acid and the majority of ent-kaurane derivatives were assessed in vitro against a panel of fourteen cancer cell lines, of which allylic alcohols were shown to be the most active compounds. The good in vitro antimalarial activity and the higher selectivity index values observed for some ent-kaurane epoxides against the chloroquine-resistant W2 clone of Plasmodium falciparum indicate that this class of natural products may provide new hits for the development of antimalarial drugs.

Euglobal-like compounds from the genus Eugenia

Two regioisomeric meroterpenoids, Eugenial A and B, have been isolated from the fruits of Eugenia multiflora and their structures established on the basis of NMR evidences. They possess a phloroglucinol-monoterpene structure similar to the euglobals occurring in the sister genus Eucaliptus. A simple method to distinguish between regioisomeric pairs was pointed.

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.

Seasonal changes in American mink (Neovison vison) signs related to Eurasian otter (Lutra lutra) presence

No Abstract available

Synthesis, characterisation, and antineoplastic cytotoxicity of hybrid naphthohydroquinone–nucleic base mimic derivatives

From a partially degraded Diels–Alder adduct of α-myrcene and 1,4-benzoquinone, several model compounds belonging to a new series of 1,4-naphthohydroquinone derivatives have been prepared. Phenyl, pyridyl, imidazolyl and some nucleic base mimic heterocycles have been attached to the naphthohydroquinone system through linkers of different size and type, leading to potentially antineoplastic hybrid structures. The new compounds have been evaluated in vitro for their cytotoxicity against cultured human cancer cells of A-549 lung carcinoma, HT-29 colon adenocarcinoma and MDA-MB-231 breast carcinoma. GI50 values ranged in the μM level.