Multidimensional optimization of promising antitumor xanthone derivatives

A promising antitumor xanthone derivative was optimized following a multidimensional approach that involved the synthesis of 17 analogues, the study of their lipophilicity and solubility, and the evaluation of their growth inhibitory activity on four human tumor cell lines. A new synthetic route for the hit xanthone derivative was also developed and applied for the synthesis of its analogues. Among the used cell lines, the HL-60 showed to be in general more sensitive to the compounds tested, with the most potent compound having a GI₅₀ of 5.1 μM, lower than the hit compound. Lipophilicity was evaluated by the partition coefficient (K_p) of a solute between buffer and two membrane models, namely liposomes and micelles. The compounds showed a log K_p between 3 and 5 and the two membrane models showed a good correlation (r² = 0.916) between each other. Studies concerning relationship between solubility and structure were developed for the hit compound and 5 of its analogues.     

New steroid and other compounds from non-polar extracts of Clusia burle-marxii and their chemotaxonomic significance

Phytochemical investigation of the non-polar extract of Clusia burle-marxii led to the identification of a new steroid (1), along with friedelinol (2), β-sitosterol (3), friedelin (4), stigmast-5-en-3β,7β-diol (5), stigmast-5-en-3β,7α-diol (6), stigmasterol (7), sitostenone (8), betulinic acid (9), butyrospermol (10), euphol (11), betulin aldehyde (12), 2,2-dimethyl-5-hydroxy-7-phenyl-chromane (13), 6-deoxyisojacareubin (14), padiaxanthone (15) and betulonic acid (16). This is the first report of the identification of compounds 5, 6 and 10 in the family, the first report of compounds 14 and 15 in the genus, and the first report of compounds 2, 3, 7, 8, 12, 16 in the species. Chemotaxonomic significance of these compounds is described herein.     

Xanthones from the heartwood of Garcinia mangostana

Twelve xanthones were isolated from the hexane extract of the heartwood of Garcinia mangostana from Myanmar. Their structures were determined using 1D and 2D NMR techniques     

Homoisoflavonoids and xanthones from the tubers of wild and in vitro regenerated Ledebouria graminifolia and cytotoxic activities of some of the homoisoflavonoids

Eleven homoisoflavonoids and two xanthones were isolated and characterized from the bulbs of Ledebouria graminifolia. Five of the homoisoflavonoids are new compounds and were identified as: 5-hydroxy-7-methoxy-3-(4'-hydroxybenzyl)-4-chromanone, 5-hydroxy-6,7-dimethoxy-3-(4'-hydroxybenzyl)-4-chromanone, 5,7,8-trimethoxy-3-(4'-hydroxybenzyl)-4-chromanone, 5-hydroxy-3',4',7-trimethoxyspiro[2H-1-benzopyran-7'-bicyclo[4.2.0]octa-trien]-4-one, 5,7-dihydroxy-3',4'-dimethoxyspiro[2H-1-benzopyran-7'-bicyclo[4.2.0]octa-trien]-4-one. Structures were elucidated by extensive 1D, and 2D NMR spectroscopy and HRMS. A method for tissue culture was developed and the bulbs of mature plants were found to contain all the compounds isolated from the wild specimens of L. graminifolia.     

Xanthones from the bark of Garcinia merguensis

The bark of Garcinia merguensis yielded 10 xanthones, merguenone, 1,5-dihydroxy-6'-methyl-6'-(4-methyl-3-pentenyl)-pyrano(2',3':3,2)-xanthone, subelliptenone H, 8-deoxygartanin, rheediaxanthone A, morusignin G, 6-deoxyjacareubin, 1,3,5-trihydroxy-4,8-di(3-methylbut-2-enyl)-xanthone, rheediachromenoxanthone and 6-deoxyisojacareubin. The structure of merguenone was determined using spectroscopic techniques, mainly 1D and 2D NMR spectroscopy.     

A New DNA‐Intercalative Cytotoxic Allylic Xanthone from Swertia corymbosa

Phytochemical investigation of the CHCl₃ fraction of Swertia corymbosa resulted in the isolation of a new 3‐allyl‐2,8‐dihydroxy‐1,6‐dimethoxy‐9H‐xanthen‐9‐one ( 1 ), along with four known xanthones, gentiacaulein ( 3 ), norswertianin ( 4 ), 1,3,6,8‐tetrahydroxyxanthone ( 5 ), and 1,3‐dihydroxyxanthone ( 6 ). Structure of compound 1 was elucidated with the aid of IR, UV, NMR, and MS data, and chemical transformation via new allyloxy xanthone derivative ( 2 ). Compounds 1 – 6 exhibited various levels of antioxidant and anti‐α‐glucosidase activities. Absorption and fluorescence spectroscopic studies on 1 – 6 indicated that these compounds could interact with calf thymus DNA (CT‐DNA) through intercalation and with bovine serum albumin (BSA) in a static quenching process. Compound 1 was found to be significantly cytotoxic against human cancer cell lines HeLa, HCT116, and AGS, and weakly active against normal NIH 3T3 cell line.     

Geranylated tetraoxygenated xanthones from the pericarp of Garcinia pedunculata

Three new xanthones, pedunxanthones D-F (1–3), along with ten known compounds, were isolated from a chloroform extract of the pericarp of Garcinia pedunculata. Their structures were determined using spectroscopic techniques. Cytotoxicity against HeLa and NCI-H460 cells of the isolated compounds using an SRB assay was evaluated with pedunxanthone D (1) as the most active compound (IC₅₀ 24.9 ± 0.4 and 26.1 ± 1.5 μg/ml, respectively).     

Diversity of non-reducing polyketide synthase genes in the Pertusariales (lichenized Ascomycota): a phylogenetic perspective

Lichenized fungi synthesize a great variety of secondary metabolites. These are typically crystalline compounds, which are deposited extracellularly on the fungal hyphae. While we know a lot about the chemical properties and structures of these substances, we have very little information on the molecular background of their biosynthesis. In the current study we analyze the diversity of non-reducing polyketide synthase (PKS) genes in members of the lichenized Pertusariales. This order primarily contains fully oxidized secondary metabolites from different substance classes, and is chemically and phylogenetically well studied. Using a degenerate primer approach with subsequent cloning we detected up to five non-reducing PKS sequences in a single PCR product. Eighty-five new KS sequence fragments were obtained for this study. Analysis of the 157 currently available fungal KS sequence fragments in a Bayesian phylogenetic framework revealed 18 highly supported clades that included only lichenized taxa, only non-lichenized taxa, or both. Some Pertusarialean groupings of PKS sequences corresponded partly to phylogenetic groupings based on ribosomal DNA. This is reasonable, because a correlation between well-supported phylogenetic lineages and the occurrence of secondary metabolites in the Pertusariales has been observed before. However, no clear linkage was found between the PKS genes analyzed and the ability to produce a particular secondary substance. Several PKS clades did not reveal obvious patterns of secondary compound distribution or phylogenetic association. Compared with earlier phylogenetic analyses of KS sequences the increased sampling in the current study allowed us to detect many new groupings within the fungal non-reducing PKSs.     

Xanthone derivatives from Cratoxylum cochinchinense roots

Two xanthones and two caged-prenylated xanthones, named cochinchinones A-D, respectively, and a synthetically known caged-prenylated xanthone, together with seven known compounds were isolated from the roots of Cratoxylum cochinchinense (Lour.) Blume. Their structures were assigned on the basis of analyses of spectroscopic data. Some of the compounds exhibited effective antioxidative properties.