Cyclic Systems Distribution Along Similarity Measures: Insights for an Application to Activity Landscape Modeling.

The emerging concept of the activity landscape has been widely applied for structureactivity relationships (SAR) characterization. Since chemical space representation plays a crucial role in activity landscape modeling, an adequate selection of similarity measures is desirable. Herein a set of 658 cyclooxygenase inhibitors were structurally analyzed using 12 molecular similarity representations and two levels of chemotype classification. Then, three uncorrelated similarity measures and mean similarity (obtained with data fusion) were combined with chemotype information using the herein proposed chemotypesimilarity graphs. Chemotype-similarity graphs showed the cumulative distribution of molecular pairs with the same and different chemotype along similarity values; leading to establish an interpretable, quantitative and activity independent threshold in similarity measures based on chemotype distributions. This approach gave additional information to similarity measures and can be considered as an interpretable criterion to define high and low similar compounds. The results were applied to model the activity landscape using StructureActivity Similarity (SAS)-like maps. Some examples of pairs in each region of the SAS-like maps were analyzed which showed valuable SAR information for cyclooxygenase inhibitors.

Synthesis, cytotoxic and antioxidant evaluations of amino derivatives from perezone.

A series of eight amino derivatives (3a-h) from perezone 1 were prepared by nucleophilic addition of bioactive amines v.gr. melatonin, acetyl tryptamine, tryptophan and other amino acids esters (valine, leucine and methionine). Their structures were elucidated by spectroscopy data. The cytotoxic evaluation against four human tumor cell lines PC-3, K-562, HCT-15 and SKLU-1 was performed as well as the TBARS assay for antioxidant activity. The results suggest that 1 and its isomer 4 were highly active against all cell lines, 4 was twice as potent than 1 against PC-3 and HCT-15. The derivative 3a (IC(50)=7.5 ± 0.3 µM) was more active than 1 against HCT-15 whereas 3h was selective against K-562 with IC(50)=4.5 ± 0.4 µM. The TBARS assay has shown that 3c with IC(50)=5.564 ± 0.24 µM is a potent antioxidant with superior effect comparing to α-tocopherol and moreover was more active than the precursor molecule 1.

(1) H and (13) C NMR characterization of new cycloartane triterpenes from Mangifera indica.

From the stem bark of Mangifera indica, seven cycloartane-type secondary metabolites were isolated. Compound 1 has been isolated for the first time from M. indica, whereas compounds 2 (2a and 2b, as an epimeric mixture), 3, and 4 are new triterpenoid-type cycloartanes. Unambiguous (13) C and (1) H NMR assignments for these compounds and the known compounds mangiferonic acid (compound 5), isomangiferolic acid (compound 6), ambolic acid (compound 7), and friedelin (compound 8) are reported; the latter because full NMR data for these compounds are not available in the literature.