Biotransformation of guttiferones, metabolites, by , an endophytic fungus isolated from its leaves.

The search for active microorganisms for the biotransformation of guttiferone A (1) and C (6) has been successfully undertaken from a collection of endophytic fungi of Symphonia globulifera. Of the twenty-five isolates obtained from the leaves, three are active and have been identified as Bipolaris cactivora. The products obtained are the result of xanthone cyclisation with the formation of two regioisomers among four possible and corresponding to 1,16-oxy-guttiferone and 3,16-oxy-guttiferone.

A Photoalkylative Fluorogenic Probe of Guttiferone A for Live Cell Imaging and Proteome Labeling in .

Guttiferone A (GA) , a polycyclic polyprenylated acylphloroglucinol (PPAP) isolated from the plant (Clusiaceae), constitutes a novel hit in antimalarial drug discovery. PPAPs do not possess identified biochemical targets in malarial parasites up to now. Towards this aim, we designed and evaluated a natural product-derived photoactivatable probe AZC-GA , embedding a photoalkylative fluorogenic motif of the 7-azidocoumarin (AZC) type, devoted to studying the affinity proteins interacting with GA in .

Guttiferone A Aggregates Modulate Silent Information Regulator 1 (SIRT1) Activity.

Natural products guttiferone A, hyperforin, and aristoforin were able to inhibit or increase SIRT1 catalytic activity, depending on protein concentration and presence of detergent. On the basis of NMR data for guttiferone A, we demonstrated that the aggregation state of the natural product played a crucial role for its interaction with the enzyme. These results are useful to interpret future in vitro structure-activity relationship studies on these natural products in the quest of their biological target(s).

Isolation of Guttiferones from Renewable Parts of Symphonia globulifera by Centrifugal Partition Chromatography.

The aim of this study was to investigate the species Symphonia globulifera, a source of polycyclic polyprenylated acyl phloroglucinols such as guttiferone A, which is known to exhibit a variety of biological activities including noticeable antileishmanial properties. Our goal was the identification and the quantification of guttiferone A in different renewable parts of S. globulifera and its preparative isolation.

Symphonia globulifera, a widespread source of complex metabolites with potent biological activities.

Symphonia globulifera has been widely used in traditional medicine and has therefore been subjected to several phytochemical studies in the American and African continents. Interestingly, some disparities have been observed concerning its metabolic profile. Several phytochemical studies of S.

Comparative LC-MS-based metabolite profiling of the ancient tropical rainforest tree Symphonia globulifera.

In the last few years, several phytochemical studies have been undertaken on the tropical tree Symphonia globulifera leading to the isolation and characterisation of several compounds exhibiting antiparasitic activities against Plasmodium falciparum, Trypanosoma brucei and Leishmania donovani. The comparative LC-MS based metabolite profiling study conducted on the tree led to the identification of compounds originating from specific tissues. The results showed that renewable organs/tissues can be used as the starting material for the production of polycyclic poly-prenylated-acylphloroglucinols, therefore reducing impacts on biodiversity.

Synthesis of novel guttiferone A derivatives: in-vitro evaluation toward Plasmodium falciparum, Trypanosoma brucei and Leishmania donovani.

The catechol pharmacomodulation of the natural product guttiferone A, isolated from the Symphonia globulifera tree, led to the semisynthesis of a collection of twenty derivatives. The ester and ether derivatives of guttiferone A were evaluated for their anti-plasmodial, trypanocidal and anti-leishmanial activities. Some compounds described below have shown potent antiparasitic activity against Plasmodium falciparum, Trypanosoma brucei and Leishmania donovani in a range from 1 to 5 μM.

Yeast-mediated xanthone synthesis through oxidative intramolecular cyclization.

Benzoylphloroglucinol derivatives are natural products showing diverse biological activities that could be modulated by structural modifications. For this purpose, we studied the biotransformation of guttiferone A and of maclurin using a combinatorial approach for screening active microorganism strains. We found a novel and unexpected yeast-catalyzed oxidation that has selectively given a new oxy-guttiferone A and norathyriol.

A new sphingolipid and furanocoumarins with antimicrobial activity from Ficus exasperata.

From the methanol extract of the stem bark of Ficus exasperata, a new sphingolipid named Ficusamide, (2S,3S,4R,11E)-2-[(2',3'-dihydroxyhexacosanoylamino)]-11-octadecene-1,3,4-triol (1), along with three known furanocoumarins, (S)-(-) oxypeucedanin hydrate (2), (R)-(+) oxypeucedanin hydrate (3), bergapten (5-methoxypsoralen) and six other known compounds, were isolated. Their structures were characterized basing on spectroscopic methods and chemical evidence. Compounds (1-3) were analyzed for their antimicrobial activity.

Cytotoxic prenylated acetophenone dimers from Acronychia pedunculata.

Three new acetophenone dimers or Acronychia-type acetophenones, acropyrone (1), acropyranol A (2), and acropyranol B (3), were isolated from the trunk bark of Acronychia pedunculata and structurally characterized, together with four known acetophenone dimers, acrovestone (4), acrovestenol (5), acrofolione A (6), and acrofolione B (7), the acetophenone monomer acronyline (8), and four furoquinoline alkaloids. The chemical structures of the new isolated compounds were elucidated unambiguously by spectroscopic data analysis. The cytotoxic activities of the isolated acetophenone dimers were evaluated against the DU145 prostate and A2058 melanoma human cancer cell lines as well as the NHDF normal cell line.

Antimicrobial activity of the methanolic extract and compounds from the stem bark of Drypetes tessmanniana.

Objective: To evaluate the antimicrobial activity of the methanol extract from the stem bark of Drypetes tessmanniana, fractions (DTB1-5) as well as compounds [friedelin (2), 3,7-dioxofriedelane (3), 3,15-dioxofriedelane (4), 3beta- O-(E)-3,5-dihydroxycinnamoyl-11-oxo-olean-12-ene (6), and 3beta,6alpha-dihydroxylup-20(29)-ene (7).

Methods: Agar disc diffusion was used to determine the sensitivity of the above samples, whilst the microdilution method was used for the determination of the minimal inhibitory concentration (MIC) and the minimal microbicidal concentrations (MMC).

Results: The diffusion test showed that the crude extract was able to prevent the growth of all tested organisms.

Synthesis and cytotoxic activity of psorospermin and acronycine analogues in the 3-propyloxy-acridin-9(10H)-one and -benzo[b]acridin-125H-one series.

In order to explore the structure-activity relationships in the acronycine and psorospermin series, simplified analogues of the highly cytotoxic (+/-)-(2R*,1'R*)-5-methoxy-11-methyl-2-(2-methyloxiran-2-yl)-1,2-dihydro-11H-furo[2,3-c]acridin-6-one and (+/-)-(2R*,1'R*)-5-methoxy-13-methyl-2-(2-methyloxiran-2-yl)-1,2-dihydro-13H-benzo[b]furo[3,2-h]-acridin-6-one lacking the fused furan ring, including 3-allyloxy-1-methoxy-10-methyl-acridin-9(10H)-one, 3-allyloxy-1-methoxy-5-methyl-benzo[b]acridin-12(5H)-one, the corresponding epoxides, and related dihydrodiol esters and diesters were prepared. Only the simplified oxirane compounds displayed significant antiproliferative activity compared to the parent compounds. The oxirane alkylating unit appears indispensible to observe significant antiproliferative activity in both series, but the presence of the angularly fused furan ring does not appear as a crucial structural requirement to observe significant cytotoxic activity.

Antitumor psoropermum xanthones and sarcomelicope acridones: privileged structures implied in DNA alkylation.

Fused isopropylfuran and dimethylpyran units are privileged structures present in numerous bioactive natural products exemplified, in the field of anticancer drugs, by the furanoxanthone psorospermin and the pyranoacridone acronycine. Psorospermin binds to the N-7 position of the guanine units in the presence of topoisomerase II. In contrast, acronycine derivatives such as cis-1,2-diacetoxy-1,2-dihydrobenzo[b]acronycine alkylate the 2-amino group of DNA guanine residues in the minor groove.

Oxidative burst inhibitory and cytotoxic indoloquinazoline and furoquinoline alkaloids from Oricia suaveolens.

Two new β-indoloquinazoline alkaloids, orisuaveoline A (1) and orisuaveoline B (2), two new furoquinoline alkaloids, quinosuaveoline A (5) and quinosuaveoline B (6), and 12 known compounds were isolated from Oricia suaveolens. The structures of the new compounds were deduced by spectroscopic studies. The absolute configuration of nkolbisine (4) was also determined.

Synthesis, cytotoxic activity, and mechanism of action of furo[2,3-c]acridin-6-one and benzo[b]furo[3,2-h]acridin-6-one analogues of psorospermin and acronycine.

Compounds possessing the epoxyfuran system present in the natural cytotoxic dihydrofuroxanthone psorospermin (4) fused onto the acridone or benzo[b]acridone chromophores present in the antitumor acronycine (1) and S23906-1 (3) were prepared. The basic furoacridone and benzofuroacridone cores bearing an isopropenyl substituent at a convenient position were synthesized by condensation of 1,3-dihydroxyacridone (7) or 1,3-dihydroxybenz[b]acridin-12(5H)-one (9) with (E)-1,4-dibromo-2-methylbut-2-ene. In both series, the (2R*,1'S*) epoxides, with the same relative configuration as psorospermin, were the most active compounds, exhibiting cytotoxic properties with IC50 values in the 10-100 nM range.

New triterpenoids from the stem barks of Drypetes tessmanniana.

The MeOH extract of the stem barks of Drypetes tessmanniana (Euphorbiaceae) afforded two new triterpene derivatives characterized as 3beta-O-(E)-3,5-dihydroxycinnamoyl-11-oxo-olean-12-ene and 3beta,6alpha-dihydroxylup-20(29)-ene together with seven known compounds. Their structures were established on the basis of spectral analysis.

alpha-Glucosidase inhibitory constituents from stem bark of Terminalia superba (Combretaceae).

The CH(2)Cl(2)/CH(3)OH (1/1) extract of the dried stem bark of Terminalia superba afforded two compounds, (7S,8R,7'R,8'S)-4'-hydroxy-4-methoxy-7,7'-epoxylignan and meso-(rel 7S,8R,7'R,8'S)-4,4'-dimethoxy-7,7'-epoxylignan along with 11 known compounds. The structures of the compounds were established by analysing the spectroscopic data and also comparing it with the data of previously known analogues. All the isolated compounds were evaluated for their glycosidase inhibition activities.

Synthesis, antitumor activity, and mechanism of action of benzo[a]pyrano[3,2-h]acridin-7-one analogues of acronycine.

Twenty-two derivatives belonging to the cis-1,2-diacyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[a]pyrano[3,2-h]acridin-7-one series were synthesized in nine steps starting from 3,5-dimethoxyacetanilide (5) and 2-methoxy-1-naphthalenecarboxylic acid (7). Most of them exhibited submicromolar cytotoxicity when tested against murine leukemia (L1210) and human epidermoid carcinoma (KB-3-1) cell lines. The cytotoxic activity correlated strongly with the ability of the compounds to form covalent adducts with purified DNA.

Synthesis of polyhydroxylated piperidines and evaluation as glycosidase inhibitors.

A series of 16 new chiral nonracemic polyhydroxylated piperidines was synthesized utilizing several chiral beta-amino-alcohols. They act as a nitrogen source, chirality inducer and iminium stabilizer, in the desymmetrization of meso-trihydroxylated glutaraldehyde. The biological activity of these compounds towards several glycosidases (alpha-D-glucosidase, alpha-D-mannosidase, alpha-L-fucosidase) has been evaluated.

7-O-6'-O-malonylcachinesidic acid, a new macrocyclic iridoid ester of malonic acid from the Tunisian plant Ajuga pseudoiva.

A new iridoid glucoside, 7-O-6'-O-malonylcachinesidic acid (1), was isolated from the leaves of Ajuga pseudoiva and characterized as its triacetyl derivative (1a). Its structure was established by spectroscopic methods and showed an unusual feature, in which an alcoholic function of the iridoid moiety and the primary alcohol of a glucopyranose unit form a 13-membered heterocycle with malonic acid.