Structure-activity relationship studies of the phytotoxic properties of the diterpenic moiety of breviones.

BACKGROUND: Brevianes are a family of bioactive meroterpenoids originally described in fungi of the family Penicillium. These compounds have attracted a great deal of interest not only because of their unusual skeleton, suggesting a mixed mevalonate and polyketide biogenetic pathway, and their unusual oxa-spiro ring fused to an α-pyrone, but also because of the bioactivities shown by many members of this family. RESULTS: During the course of a project aimed at the total synthesis of natural breviones A to E, the authors were able to synthesise the diterpenic moiety of brevianes and abeo-brevianes. As a result, a collection of 25 compounds were synthesised and tested for bioactivity by two different bioassays. The bioassays used were etiolated wheat coleoptiles (Triticum aestivum) and seedlings in petri dishes. The plant species tested in the seedling bioassay were the commercial dicots lettuce and cress and the monocot weeds Echinochloa crus-galli and Lolium rigidum. CONCLUSIONS: The results clearly show that expanded phenanthrene-like compounds corresponding to the diterpenic moiety of abeo-brevianes are more selective towards E. crus-galli in comparison with L. rigidum. Such selectivity can reach up to one order of magnitude (200-fold) and makes some of the compounds good candidates as leads for the development of more specific herbicides.

New chemical clues for broomrape-sunflower host-parasite interactions: synthesis of guaianestrigolactones.

A comparative structure-activity relationship (SAR) study has been conducted with several guaianolide sesquiterpene lactones (SLs) as inducers of the germination of sunflower broomrape (Orobanche cumana) seeds. Compounds were selected and synthesized to study the influence of the lactone-enol-gamma-lactone moiety on the selectivity of SLs toward the stimulation of sunflower broomrape germination. The results clearly illustrate that SLs are recognized only by O. cumana, while the introduction of a strigol-like second lactone moiety in the guaianolide backbone results in the loss of specificity and hence the germination of other broomrape species. We have named this new class of compounds guaianestrigolactones (GELs).

Antifungal activity of a new phenolic compound from capitulum of a head rot-resistant sunflower genotype.

In a previous study, we observed that bract and corolla extracts from a Sclerotinia sclerotiorum-resistant sunflower contained high amounts of the known coumarins scopoletin, scopolin, and ayapin. There was a correlation between coumarin concentration and disease resistance. Thin layer chromatography showed higher concentrations of three other compounds in the resistant genotype when compared to the susceptible. A bioassay-directed purification that used column chromatography and HPLC allowed the isolation of a new compound, 3-acetyl-4-acetoxyacetophenone, and known compounds, demethoxyencecalin and 3-acetyl-4-hydroxyacetophenone. Structures were assigned from spectral data, and bioactivities were characterized by in vitro bioassays against S. sclerotiorum. The new compound, 3-acetyl-4-acetoxyacetophenone, had an antifungal activity similar to the coumarin ayapin, previously described as a potent Sclerotinia inhibitor. The speed and simplicity by which these compounds can be detected make them suitable for use in screening procedures that may identify genotypes with valuable levels of resistance. A screening of seven sunflower genotypes in a field experiment showed a correlation between these compounds and resistance to Sclerotinia.

Evolution and current status of ecological phytochemistry.

Phytochemical studies have experienced a great deal of change during the last century, not only regarding the number of compounds described, but also in the concept of phytochemistry itself. This change has mainly been related to two key points: the methodologies used in phytochemical studies and the questions regarding 'why secondary metabolites appeared in plants and in other living organisms?' and 'what is their role?'. This transformation in the field has led to new questions concerning such different subjects as evolution, paleobotany, biochemistry, plant physiology and ethnography. However, the main issue is to clarify the role that secondary metabolites play in the plant (and other organisms) and whether the resources invested in their production (C and N allocation, genes encoding their biogenetic pathways, specific enzymes, energy-rich molecules such as ATP and NADPH) have or lack a reasonable reward in terms of advantages for survival. Consequently, in this review the main emphasis will be placed on two subjects related to the evolution of phytochemical studies. The first aim is to describe briefly the influence that the development of the methodologies needed for compound isolation and structure elucidation have had on the field of phytochemistry. The second area to be covered concerns the new theories addressing the role of secondary metabolites from an ecological point of view: co-evolution of plants and their potential enemies (phytophagous insects, microbes, herbivores and other plants), chemical plant defence, adaptative strategies of phytophagues to plant toxins (among them sequestration will be briefly mentioned), and models and theories for carbon and nitrogen allocation. Some final remarks are made to summarize our opinion about the immediate future of phytochemical ecology and phytochemical studies.

Allelopathy--a natural alternative for weed control.

Allelopathy studies the interactions among plants, fungi, algae and bacteria with the organisms living in a certain ecosystem, interactions that are mediated by the secondary metabolites produced and exuded into the environment. Consequently, allelopathy is a multidisciplinary science where ecologists, chemists, soil scientists, agronomists, biologists, plant physiologists and molecular biologists offer their skills to give an overall view of the complex interactions occurring in a certain ecosystem. As a result of these studies, applications in weed and pest management are expected in such different fields as development of new agrochemicals, cultural methods, developing of allelopathic crops with increased weed resistance, etc. The present paper will focus on the chemical aspects of allelopathy, pointing out the most recent advances in the chemicals disclosed, their mode of action and their fate in the ecosystem. Also, attention will be paid to achievements in genomics and proteomics, two emerging fields in allelopathy. Rather than being exhaustive, this paper is intended to reflect a critical vision of the current state of allelopathy and to point to future lines of research where in the authors' opinion the main advances and applications could and should be expected.

Application of Hansch's model to guaianolide ester derivatives: a quantitative structure-activity relationship study.

A quantitative structure-activity study to evaluate the effect of lipophilia/aqueous solubility on etiolated wheat coleoptiles elongation has been carried out with 34 guaianolides having different numbers of hydroxyl groups and ester side chains of variable length and structure: linear, branched, aromatic, and unsaturated. Compounds have been tested in a range of concentrations between 10 and 1000 microM. Data show a strong influence of lipophilia, expressed as logP values. Specially, data from alkylic side chain ester derivatives adjust to the mathematical model based on Hansch's transport theory; hence, a quantitative structure-activity relationships (QSAR) correlation with a high degree of reliance is provided. Moreover, all active compounds fit the Lipinski's rule of five. Also, the presence of additional hydroxyl groups and their derivatives in the basic skeleton does not affect the mode of action but greatly influences the activity, as they modify the transport through membranes and aqueous phases. Finally, a second hydroxyl group enhances differences of activity between alkylic side chain derivatives by increasing differences in van der Waals interactions.

SAR studies of sesquiterpene lactones as Orobanche cumana seed germination stimulants.

Studies of the structure-activity relationship (SAR) directed to evaluate the effect of several sesquiterpene lactones (SL) as germination stimulants of three Orobanche spp. (O. cumana, O. crenata, and O. ramosa) have been achieved. Results are compared with those obtained in the same bioassay with an internal standard, the synthetic analogue of strigol GR-24. A high specificity in the germination activity of SL on the sunflower parasite O. cumana has been observed, and a relationship between such activity and the high sunflower SL content is postulated. Molecular properties of the natural and synthetic germination stimulants (GR-24, GR-7, and Nijmegen-1) and SL have been studied using MMX and PM3 calculations. Consequently, comparative studies among all of them and their activities have been made. SL tested present similarities in molecular properties such as the volume of the molecule and the spatial disposition of the carbon backbone to the natural germination stimulant orobanchol. These properties could be related to their biological activity.