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2-Aminothieno[3,2-d]pyrimidin-4-ones were synthesized in one step by condensation of 3-amino(benzo)thiophene carboxylate with chloroformamidine hydrochloride.

For the first time arv unsymmetrical 2,2′-6′2″-terpyridine carry two carboxylic acids has been prepared using Hantzsch's method for pyridine ring formation and furan as a latent carboxylic group.

We present a flow cytometry technique to evaluate the antioxidative properties of molecules on living cells, using a stable murine-murine hybridoma (Mark 3) cell line routinely cultured. Using this technique, intracellular superoxide anions and peroxides were evaluated with dihydrorhodamine (DHR-123) and dichlorofluorescein diacetate (DCFH-DA), respectively. When cells were first incubated for 10 min with either H(2)O(2) or the xanthine (X)/xanthine oxidase (XO) system, this flow cytometric technique was capable of evaluating the oxidative stress on cells. Twenty-one new analogues of ellipticine were synthesized and tested for their antioxidative properties compared to vitamin E and Ebselen used as references. A good statistical reflection of the antioxidative activities of these molecules was achieved by analyzing 35 000 cells in each experiment. Among them, the selenated molecule 18 was found to be 10 times more active than Ebselen but 10 000 times less active than vitamin E. Moreover, eight compounds showed glutathione peroxidase-like activities.

5-Methylbenzo[b]thieno[2,3-c]isoquinolines and 5-methylbenzo[b]seleno[2,3-c]isoquinolines 11b,c have been prepared by Bischler-Napieralski cyclization of 2-acetamido-3-phenylbenzo[b]heteroarenes.

We describe herein a new amination procedure of weakly activated heterocyclic bromo derivatives in aqueous media. The base catalysed mechanism of this reaction is also confirmed. Moreover, the application of this strategy to the preparation of amino furans and selenophenes is outlined.

A one-pot procedure was developed to prepare new 2-aryl-5-nitrothiophenes efficiently from bromonitromethane and 3-chloro-3-aryl-propenals. Nitrothiophenes were synthesized in good yields with a simple and easy workup procedure.

A series of new carbazolo[2,1-a]carbazoles was synthesized from 4-oxo-1,2,3,4-tetrahydrobenzo[a]-carbazole derivatives.

The synthesis of α-substituted β-aryl-β-haloacroleins by two different pathways is presented. The determination of their stereochemistry by NOE experiments is reported for the first time. Furthermore, we describe the preparation of 2-en-4-ynecarbaldehydes and access to rubrolide derivatives from β-aryl-β-haloacroleins.

Thionation of o-halobenzanilides was carried out in the presence of Lawesson's reagent. Subsequently, the formed thio-amides reacted with cesium carbonate to give the corresponding benzothiazole derivatives in the same pot.

A synthetic route to prepare 4-methylumbelliferyl-β-D-glucopyranosiduronic acid (MUG) from 4-methylumbelliferyl-β-D-glucopyranoside (MUGluc) was developed. The primary hydroxyl group in MUGluc was protected by tritylation followed by acetylation of secondary hydroxyls. The triphenylmethyl group was selectively removed by treatment with iodine-methanol in benzene and the free hydroxyl was transformed into the carboxylic acid by phase-transfer oxidation with sodium hypochlorite and TEMPO as catalyst. Finally, the acetate groups were removed by reaction with barium methoxide in methanol to afford the MUG with an overall yield of 37% from the MUGluc.

An efficient two steps procedure for the synthesis of 1-acetyl-1H-indol-3-yl acetates, starting from 2-chlorobenzoic acids, was developed and in general, moderate to good yields were obtained

A direct access to pentacyclic molecules via Fischer Indole Synthesis starting from tricyclic ketones is described.

Pyridocarbazole moiety is found for example in alkaloids from the ellipticine 1 series and indolocarbazole in tjipanozole 2 and staurosporine 3.

Coumarin derivatives were prepared using zirconyl chloride octahydrate (1%) as a Pechmann catalyst, either neat or in some cases employing small volumes of ethanol as solvent. As result of this work, coumarins were obtained in moderate to good yields.

Sulfated zirconia (1%) was employed as Pechmann’s catalyst without solvent or in some cases using a small amount of ethanol to obtain coumarins in moderate to good yields. With this procedure, no significant acidic waste was obtained and an environmental friendly alternative to obtain coumarins is provided.

International audience; A series of 5-aryl-2-(3-thienylamino)-1,3,4-thiadiazoles 3a-m were synthesized in good yields in two steps starting from thiophen-3-isothiocyanates. Those compounds as well as the thiosemicarbazide intermediates 2a-m were screened for their antiproliferative activity against a panel of six cancer cell lines. Among them, two 5-aryl-2-(3-thienylamino)-1,3,4-thiadiazoles (3f and 3i) have shown very interesting results with IC50 < 10 mu M on three cell lines.

Indenoindoles and their isomers cyclopentacarbazoles represent a wide class of synthetic and natural compounds. The great interest of these structures in (bio)organic chemistry is due to the use of various building blocks to get the elemental four ring structure. Depending on the synthetic route chosen, the chemists can achieve a large number of regioisomers. Each regioisomer can be considered as a template for specific functionalizations. Therefore, this mini-review aims (i) to present an overview on how to access this large family of heterocyclic compounds and (ii) to discuss their various biological applications and drug development in oncology (e.g. kinases), in CNS disorders (e.g. Alzheimer's disease), in endocrinology (e.g. hormone replacement therapy) and oxidative stress (e.g. organ preservation). Past and present works will be presented through the systems 6-5-5-6 and 6-5-6-5 (combination of 6-membered and 5-membered rings).

In this chapter, bromelain, a crude multi-component extract isolated from the stems of the pineapple plant, takes us on a tour through rather unusual therapeutic approaches and pharmacological mechanisms. Bromelain acts on several targets that address edematous, inflammatory, and immunological processes. Therefore, many indications were treated with or are conceivable to be treated by use of this phytomedicine. Bromelain teaches us that we should keep an open mind toward at first sight exotic therapeutic approaches. A plea for the use of the potential of natural products that are well established in medical therapy for decades or even centuries.

It happens in Nature that compounds with interesting biological activity are formed of individual blocks of different structures, which are generally active by themselves. For example, different acids such as quinic acid or shikimic acid, are found to be conjugated to caffeic acid. In these cases the combination is the result of a biosynthetic process. At the same time, chemists were interested in melting together natural products known for specific activity in a way to obtain a multiple shot for the biological effect or also, sometimes, to enhance in vivo distribution. This chapter presents some examples of the research done in this way with a special focus on redox active compounds.

International audience; Histone deacetylases (HDACs) are well-established, promising targets for anticancer therapy due to their critical role in cancer development. Accordingly, an increasing number of HDAC inhibitors displaying cytotoxic effects against cancer cells have been reported. Among them, a large panel of chemical structures was described including coumarin-containing molecules. In this study, we described synthesis and biological activity of new coumarin-based derivatives as HDAC inhibitors. Among eight derivatives, three compounds showed HDAC inhibitory activities and antitumor activities against leukemia cell lines without affecting the viability of peripheral blood mononuclear cells from healthy donors.

In this chapter, bromelain, a crude multi-component extract isolated from the stems of the pineapple plant, takes us on a tour through rather unusual therapeutic approaches and pharmacological mechanisms. Bromelain acts on several targets that address edematous, inflammatory, and immunological processes. Therefore, many indications have been treated with or are conceivable to be treated by use of this phytomedicine. Bromelain teaches us that we should keep an open mind toward at first sight exotic therapeutic approaches. A plea for the use of the potential of natural products that are well established in medical therapy for decades or even centuries.

International audience; Cancer cells display an overproduction of reactive oxygen species resulting from an exaggerated intrinsic oxidative stress. However, the concept of deleterious oxidants versus beneficial antioxidants has recently evolved. Indeed, molecules like natural coumarins have shown anti-oxidant or pro-oxidant properties depending on their intracellular concentration. Therefore, we have investigated the structure-activity relationship of a variety of coumarin derivatives in terms of cytotoxicity towards human and murine carcinoma cell lines (HT29, HepG2, A549, MCF7, OVCAR and CT26). Amongst those compounds, (E)-7-methoxy-4-(3-oxo-3phenylprop- 1-enyl)-2H-chromen-2-one and (E)-7-hydroxy-4-(3-(4-hydroxyphenyl)-3-oxoprop-1-enyl)-2H-chromen-2-one displayed the most potent cytotoxic effect on colon cancer cells, CT26, (IC50= 4.9 mu M) linked to their pro-oxidant properties. Those compounds triggered the in vitro production of reactive oxygen species by tumor cells, leading to their death through a necrotic process. In vivo, molecules also slowed down tumor growth by 65.7% and 35.4%, respectively, without inducing significant side effects.

International audience; Not widely distributed in nature, aurones, (Z)-2-benzylidene-benzofuran-3(2H)-ones, are one of the less common and lesser-known representatives of a flavonoid subclass. Nevertheless, they exhibit a strong and broad variety of biological activities. We have combined the benzofuranone part of a classical aurone with either a chromone or a coumarin scaffold which proved to feature interesting biological activities including antimicrobial, antiviral, anticancer, anti-inflammatory and antioxidant properties. Herein we present a series of 26 novel benzofuran derivatives with the first biological results in K562 human leukemia cells showing that compounds 21b, 29b and 29c are able to induce around 24% apoptosis.

International audience; Selenium compounds play a major role in Biology, where they are often associated with pronounced antioxidant activity or toxicity. Whilst most selenium compounds are not necessarily hazardous, their often selective cytotoxicity is interesting from a biochemical and pharmaceutical perspective. We have synthesized a series of amphiphilic molecules which combine a hydrophilic seleninic acid head group - which at the same time serves as thiol-specific warhead - with a hydrophobic tail. These molecules possess a surface activity similar to the one of SDS, yet their biological activity seems to exceed by far the one of a simple surfactant (e.g. SDS) or seleninic acid (e.g. phenyl seleninic acid). Such compounds effectively haemolyse Red Blood Cells and exhibit pronounced activity against Saccharomyces cerevisiae. From a chemical perspective, the seleninic warheads are likely to attack crucial cysteine proteins of the cellular thiolstat.

International audience; A new ceramide (1) along with lupeol (2) and a mixture of β-sitosterol and stigmasterol, oleanolic acid (4), maslinic acid (5), β-sitosterol glucopyranoside (6), and trans-tiliroside (7) were isolated from Triumfetta rhomboidea (Tiliaceae). Their structures were determined on the basis of spectroscopic methods and mass spectrometry analysis, as well as by comparison of their physical and spectral data with those reported in the literature. The cytotoxic activity of crude extract, fractions, and some compounds were evaluated against human fibrosarcoma cancer cell line HT1080 using flow cytometry. The ethyl acetate fraction showed weak activity while the crude extract and the hexane and n-butanol fractions presented less than 50% of cell growth inhibition.

It is demonstrated that base promoted intramolecular condensation occurs preferentially on the adjacent nitrile group rather than at an ester or at a ketone substituent.

International audience; Driven by a multidisciplinary approach combination (Structure-Based (SB) Three-Dimensional Quantitative Structure-Activity Relationships (3-D QSAR), molecular modeling, organic chemistry and various biological evaluations) here is reported the disclosure of new thienopyrimidines 1-3 as inhibitors of KDR activity and human umbilical vein endothelial cell (HUVEC) proliferation. More specifically, compound 2f represents a new lead compound that inhibits VEGFR-2 and HUVEC at μM concentration. Moreover by the mean of an endothelial cell tube formation in vitro model 2f tartaric acid salt proved to block angiogenesis of HUVEC at μM level.

International audience; Indenoindoles and their isomers cyclopentacarbazoles represent a wide class of synthetic and natural compounds. The great interest of these structures in (bio)organic chemistry is due to the use of various building blocks to get the elemental four ring structure. Depending on the synthetic route chosen, the chemists can achieve a large number of regioisomers. Each regioisomer can be considered as a template for specific functionalizations. Therefore, this mini-review aims (i) to present an overview on how to access this large family of heterocyclic compounds and (ii) to discuss their various biological applications and drug development in oncology (e.g. kinases), in CNS disorders (e.g. Alzheimer's disease), in endocrinology (e.g. hormone replacement therapy) and oxidative stress (e.g. organ preservation). Past and present works will be presented through the systems 6-5-5-6 and 6-5-6-5 (combination of 6-membered and 5-membered rings).

A new route to 1,3-disubstituted-4, 5, 6, 7-tetrahydro benzo[c]thiophene-4-one is described starting from 1, 3-cyclohexanedione.

The in vitro growth inhibitory activity of 26 thiazoles (including 4-halogeno-2,5-disubtituted-1,3-thiazoles) and 5 thienothiazoles was assessed on a panel of 6 human cancer cell lines, including glioma cell lines. (4-Chloro-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone ( 12a ) and (4-bromo-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone ( 12b ) displayed ∼10 times greater in vitro growth inhibitory activity than perillyl alcohol (POH), which therapeutically benefits glioma patients through the inhibition of both alpha-1 Na + /K + -ATPase (NAK) and Ras oncogene activity. The in vitro cytostatic activities (as revealed by quantitative videomicroscopy) displayed by 12a and 12b were independent of the intrinsic resistance to pro-apoptotic stimuli associated with cancer cells. Compounds 12a and 12b displayed relatively similar inhibitory activities on purified guinea pig brain preparations that mainly express NAK alpha-2 and alpha-3 subunits, whereas only compound 12b was efficacious against purified guinea pig kidney preparations that mainly express the NAK alpha-1 subunit, which is also expressed in gliomas, melanomas and non-small-cell lung cancers NSCLCs.

In this work, we described the synthesis of 3-isothiocyanatoselenophenes starting from 3-aminoselenophenes (using thiophosgene). Those compounds were then converted to the corresponding thioureas in the presence of ammonium hydroxide. Cyclization in 2-aminoselenolo[3,2-d]thiazoles was achieved using DDQ. 2-Aminothieno[3,2-d]thiazoles were obtained from 3-isothiocyanatothiophenes using the same pathway.

Aurones [2-benzylidenebenzofuran-3(2H)-ones] are either natural or synthetic compounds, belonging to the flavonoid family. They are isomeric to flavones and provide a bright yellow color to the pla...

La production des especes reactives de l’oxygene (ERO) est fortement impliquee dans les mecanismes de toxicite des medicaments utilises en chimiotherapie et donc dans la generation de leurs effets secondaires. L’emploi d’agents protecteurs couples a la chimiotherapie fait donc l’objet de recherches intensives en vue d’une utilisation optimale des molecules anticancereuses. L’objectif de ce travail est de selectionner et d’isoler parmi les substances naturelles, des molecules nouvelles, presentant un pouvoir antioxydant, protecteur des cellules non cancereuses, mais n’affectant pas l’efficacite des substances anticancereuses vis-a-vis des cellules tumorales.

A method of synthesis of unsymmetrical 2,5-diarylthiophenes is descri- bed using β-chloroacroleins, prepared from acetophenones, and their condensation with sodium sulfide and various benzyl bromides

A synthesis of 3-alkyl or aryl thiophenes is described starting from malonaldehydes.

A synthesis of 2,5-parasubstituted diaryl selenophenes is described β-Aryl-β-chloro acroleins, easily prepared from substituted acetophenones and Vilsmaier-Haack reagent, are condensed with appropriate benzylbromide derivatives to give the title compounds.

1,3,2-oxathia-phospholane or -phosphorinane 2-sulfide derivatives 2 and 3 are readily accessible by reaction of the triethylammonium salts 1 of diesters of the phosphorotetrathioic acid with ω-bromo alcohols under mild conditions.

A four-step preparation of compounds containing a coumarinic moiety is presented. This synthesis involves notably a Suzuki cross-coupling reaction (performed in aqueous media) and a ring closure by formation of δ-lactone.

Thiophenes 2 can easily be synthesized in two steps by using phenyl isothiocyanate and activated methylene compounds.

Starting from carboxylic acids, a convenient three-step synthesis of aldehydes is developed as is exemplified for (Va).

The interesting approach includes Pd-catalyzed Heck coupling of the tosylates with ether (II) followed by acidic rearrangement of the resulting vinyl ether intermediate.

Title compounds (III) and (V) are formed in a one-pot procedure via Dimroth rearrangement of intermediates obtained primarily from the reaction of pyrazoles (I) with carbon disulfide and Lawesson reagent, respectively.

In continuation of an ongoing project directed to synthesize novel agonists in the glitazone class, a three-step procedure for the synthesis of title compounds (VII) is described.

Several monographs, series and articles have been published on selenophene [1–4]. These give a general overview of the nucleus synthesis. In this chapter we focus on the synthesis of hydroxy and aminoselenophenes and also describe examples of their reactivity or their transformation to different condensed heterocyclic systems.

Vilsmeier Haack reagent was found to react with alkylidenecyanoacetate to afford in one step 4.5 disubstituted 2-chloronicotinates.