Vicente P. Emerenciano

Flavonoids as chemotaxonomic markers for Asteraceae.

Flavonoids have been shown to be good taxonomic markers for Asteraceae. More than 800 compounds comprising 4700 flavonoid occurrences were included in a computational system specially made for chemotaxonomic purposes. Some implications of flavonols, flavones and other types as well as structural features of them are discussed for tribes and subtribes of Asteraceae.

Design of novel antituberculosis compounds using graph-theoretical and substructural approaches

The increasing resistance of Mycobacterium tuberculosis to the existing drugs has alarmed the worldwide scientific community. In an attempt to overcome this problem, two models for the design and prediction of new antituberculosis agents were obtained. The first used a mixed approach, containing descriptors based on fragments and the topological substructural molecular design approach (TOPS-MODE) descriptors. The other model used a combination of two-dimensional (2D) and three-dimensional (3D) descriptors. A data set of 167 compounds with great structural variability, 72 of them antituberculosis agents and 95 compounds belonging to other pharmaceutical categories, was analyzed. The first model showed sensitivity, specificity, and accuracy values above 80% and the second one showed values higher than 75% for these statistical indices. Subsequently, 12 structures of imidazoles not included in this study were designed, taking into account the two models. In both cases accuracy was 100%, showing that the methodology in silico developed by us is promising for the rational design of antituberculosis drugs.

A computer-assisted approach for chemotaxonomic studies — diterpenes in Lamiaceae

This paper describes a new computer approach for chemotaxonomic studies. The methodology employed enables the search for chemical substructures as taxonomic descriptors using an expert system built with plant natural products. The operation of the system was tested with diterpenes as taxonomic markers in Lamiaceae.

Use of self-organizing maps and molecular descriptors to predict the cytotoxic activity of sesquiterpene lactones

Some sesquiterpene lactones (SLs) are the active compounds of a great number of traditionally medicinal plants from the Asteraceae family and possess considerable cytotoxic activity. Several studies in vitro have shown the inhibitory activity against cells derived from human carcinoma of the nasopharynx (KB). Chemical studies showed that the cytotoxic activity is due to the reaction of alpha,beta-unsaturated carbonyl structures of the SLs with thiols, such as cysteine. These studies support the view that SLs inhibit tumour growth by selective alkylation of growth-regulatory biological macromolecules, such as key enzymes, which control cell division, thereby inhibiting a variety of cellular functions, which directs the cells into apoptosis. In this study we investigated a set of 55 different sesquiterpene lactones, represented by 5 skeletons (22 germacranolides, 6 elemanolides, 2 eudesmanolides, 16 guaianolides and nor-derivatives and 9 pseudoguaianolides), in respect to their cytotoxic properties. The experimental results and 3D molecular descriptors were submitted to Kohonen self-organizing map (SOM) to classify (training set) and predict (test set) the cytotoxic activity. From the obtained results, it was concluded that only the geometrical descriptors showed satisfactory values. The Kohonen map obtained after training set using 25 geometrical descriptors shows a very significant match, mainly among the inactive compounds (approximately 84%). Analyzing both groups, the percentage seen is high (83%). The test set shows the highest match, where 89% of the substances had their cytotoxic activity correctly predicted. From these results, important properties for the inhibition potency are discussed for the whole dataset and for subsets of the different structural skeletons.

Chemosystematic studies of natural compounds isolated from Asteraceae: characterization of tribes by principal component analysis

Univ Nice, Equipe Chimiometrie & Modelisat, Lab Aromes Syntheses & Interact, F-06108 Nice 2, France

A chemosystematic analysis of tribes of Asteraceae involving sesquiterpene lactones and flavonoids

Abstract The correlation of oxidation levels and skeletal specializations of sesquiterpene lactones reported to occur in genera of the Asteraceae suggest the distribution of the corresponding tribes along chemical gradients. The evolutionary polarity of these gradients was established by concomitant consideration of the evolutionary replacement of O -glycosylflavonoids by O -methylflavonoids. Information on structure and occurrence of sesquiterpene lactones as well as of flavonoids was obtained in a literature survey up to 1984.

Designing novel antitrypanosomal agents from a mixed graph-theoretical substructural approach

Chagas disease is nowadays the most serious parasitic health problem. This disease is caused by Trypanosoma cruzi. The great number of deaths and the insufficient effectiveness of drugs against this parasite have alarmed the scientific community worldwide. In an attempt to overcome this problem, a model for the design and prediction of new antitrypanosomal agents was obtained. This used a mixed approach, containing simple descriptors based on fragments and topological substructural molecular design descriptors. A data set was made up of 188 compounds, 99 of them characterized an antitrypanosomal activity and 88 compounds that belong to other pharmaceutical categories. The model showed sensitivity, specificity and accuracy values above 85%. Quantitative fragmental contributions were also calculated. Then, and to confirm the quality of the model, 15 structures of molecules tested as antitrypanosomal compounds (that we did not include in this study) were predicted, taking into account the information on the abovementioned calculated fragmental contributions. The model showed an accuracy of 100% which means that the “in silico” methodology developed by our team is promising for the rational design of new antitrypanosomal drugs.

13C NMR spectroscopy of monoterpenoids

C NMR, and their subse-quent development over the years, structure elucida-tion ofnatural products hasbecome commonpractice.As a consequence, several new isolated terpenoids,including mono-, di-, tri- and sesquiterpenes, havehad their structure established. Today studies onthousands of terpenoids have been reported but theirchemical shift data are still scattered in the literature.Much of the impetus for the study of the

Evolution of sesquiterpene lactones in angiosperms

Abstract The paper attempts to discover an outline of the evolutionary trends of sesquiterpene lactones in angiosperms. The working method involves the quantification of skeletal specialization and oxidation state of the compounds and the assignment of evolutionary advancement indices, based on such data, to taxa. In the angiosperms as a whole, sesquiterpene lactone evolution proceeds by diversification of structural types and by amplification of the oxidation state of the molecules. The opposite trend appears to operate at lower hierarchical level, in the Asteraceae. In this family, which contains most of the known compounds of the class, sesquiterpene lactone evolution follows two parallel pathways in the tribes belonging to two groups of the subfamily Asteroideae.

Self-organizing maps of molecular descriptors for sesquiterpene lactones and their application to the chemotaxonomy of the Asteraceae family.

The Asteraceae, one of the largest families among angiosperms, is chemically characterised by the production of sesquiterpene lactones (SLs). A total of 1,111 SLs, which were extracted from 658 species, 161 genera, 63 subtribes and 15 tribes of Asteraceae, were represented and registered in two dimensions in the SISTEMATX, an in-house software system, and were associated with their botanical sources. The respective 11 block of descriptors: Constitutional, Functional groups, BCUT, Atom-centred, 2D autocorrelations, Topological, Geometrical, RDF, 3D-MoRSE, GETAWAY and WHIM were used as input data to separate the botanical occurrences through self-organising maps. Maps that were generated with each descriptor divided the Asteraceae tribes, with total index values between 66.7% and 83.6%. The analysis of the results shows evident similarities among the Heliantheae, Helenieae and Eupatorieae tribes as well as between the Anthemideae and Inuleae tribes. Those observations are in agreement with systematic classifications that were proposed by Bremer, which use mainly morphological and molecular data, therefore chemical markers partially corroborate with these classifications. The results demonstrate that the atom-centred and RDF descriptors can be used as a tool for taxonomic classification in low hierarchical levels, such as tribes. Descriptors obtained through fragments or by the two-dimensional representation of the SL structures were sufficient to obtain significant results, and better results were not achieved by using descriptors derived from three-dimensional representations of SLs. Such models based on physico-chemical properties can project new design SLs, similar structures from literature or even unreported structures in two-dimensional chemical space. Therefore, the generated SOMs can predict the most probable tribe where a biologically active molecule can be found according Bremer classification.