Marie-Christine Lallemand

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. Hybrid compounds associating the acridone or benzo[b]acridone chromophore of acronycine derivatives and the epoxyfuran alkylating unit present in psorospermin also display very potent antiproliferative activities, alkylating DNA guanine units at position N-7 in the major groove, as natural xanthones belonging to the psorospermin series.

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.

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. Acrovestone (4) and acrovestenol (5) exhibited substantial cytotoxicity, with IC(50) values of 0.38 and 2.8 μM against A2058 melanoma cells as well as 0.93 and 2.7 μM against DU145 prostate cancer cells, respectively.

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. The evaluation of guttiferone A derivatives against VERO cells highlighted catechol modulations as an interesting tool to decrease the toxicity and keep the activity of this natural compound. The current study revealed new molecules as promising new antiparasitic drug candidates.

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

ObjectiveTo 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), 3β- O-(E)-3,5-dihydroxycinnamoyl-11-oxo-olean-12-ene (6), and 3β,6α-dihydroxylup-20(29)-ene (7).MethodsAgar 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).ResultsThe diffusion test showed that the crude extract was able to prevent the growth of all tested organisms. All other samples showed selective activity. The inhibitory effect of the fraction DTB2 was noted on 63.7%, that of DTB1 and DBT3 on 54.6%, whilst DTB4 and DTB5 were active on 9.1% of the 11 tested organisms. The tested compounds prevented the growth of 81.8% of the tested microbial species for compounds 3 and 4, 36.7% for compound 6, and 18.2% for compound 7. The results of the MIC determinations indicated perceptible values for DTB and compound 4 on 81.8% of the tested organisms. For other samples, MICs were detected on 0–63.7%. The lowest MIC value (78.12 μg/mL) for the crude extract and fractions (DTB2) was observed on M. audouinii. The corresponding value for isolated compounds (156.25 μg/mL) was noted with compounds 3 on S. faecalis and 4 on M. audouinii audouinii. The results of the MMC determination suggested that the microbicidal effect of most of the tested samples on the studied microorganisms could be expected.ConclusionThe methanol extract from the stem bark of Drypetes. tessmanniana (Euphorbiaceae) as well as some of the isolated compounds might be potential sources of new antimicrobial drugs.

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. globulifera have led to the identification of more than 40 compounds, including several polycyclic polyprenylated acylphloroglucinols. Biological evaluations have pointed out the promising biological activities of these secondary metabolites, mostly as antiparasitic or antimicrobial, confirming the traditional use of this plant. The purpose of this review is to describe the natural occurrence, botanical aspects, ethnomedicinal use, structure, and biogenesis, as well as biological activities of compounds isolated from this species according to their provenance.

A new and efficient electrochemical ring opening of 7-oxanorbornene systems via a modified Ritter reaction: direct approach to bicyclic valienamine analogues

Abstract Electrogenerated acids (EGA), produced by controlled potential electrolysis in acetonitrile at a platinum electrode, permitted the oxa-ring opening and the acetamidation of the 7-oxanorbornene system of 4 . It opens in one step a new route to bicyclic valienamine analogues 3 .

Polycyclic Polyprenylated Xanthones from Symphonia globulifera: Isolation and Biomimetic Electrosynthesis

Two regioisomeric polycyclic xanthones, 3,16-oxyguttiferone A (2) and 1,16-oxyguttiferone A (3), which are polyprenylated acylphloroglucinol-derived analogues, were isolated from the seeds of Symphonia globulifera, together with their presumed o-dihydroxybenzoyl precursor, guttiferone A (1). Anodic oxidation of 1 into the corresponding o-quinone species proved to be an efficient biomimetic method to generate xanthones 2 and 3 in high overall yield and to confirm their structures. Both compounds displayed cytotoxicity against the HCT 116 colon carcinoma cell line with IC₅₀ values of 8 and 3 μM, respectively.

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. To the best of our knowledge, there is no data concerning its mechanism of action. Consequently, it is particularly interesting to isolate it in gram quantities in order to establish structure activity relationship studies. After performing high-performance liquid chromatography profiles detecting the presence of guttiferone A and proceeding to its quantification, a centrifugal partition chromatography methodology using a two-phase solvent system of cyclohexane/ethyl acetate/methanol/water (20 :  1 :  20 : 1, v/v/v/v) was applied to each extract. In conclusion, a centrifugal partition chromatography system has been developed to ensure a fast, reliable, and scalable way to isolate, with a high level of purity, guttiferone A from five renewable parts of S. globulifera. Moreover, this methodology can be extended to the isolation of other polycyclic polyprenylated acyl phloroglucinols such as guttiferones B, C, and D.

A prenylated acridone alkaloid and ferulate xanthone from barks of Citrus medica (Rutaceae)

Abstract A new prenylated acridone alkaloid, medicacridone (1), and a new ferulate xanthone, medicaxanthone (5), together with 11 known compounds were isolated from the methanol extract of the bark of the Cameroonian medicinal plant Citrus medica. The structures of all compounds were determined by comprehensive analyses of their 1D and 2D NMR, mass spectral (EI and ESI) data, chemical reactions, and comparison with previously known analogues. The agar diffusion test delivered low to missing antimicrobial activities, corresponding with MICs > 1 mg mL–1, while compounds 1–6 and atalantoflavone (9) displayed weak cytotoxic activity against the human Caucasian prostate adenocarcinoma cell line PC-3, with IC50 values ranging from 60.5 to 80.0 μm versus doxorubicine with IC50=0.9 μm.