Pascal Pigeon

École nationale supérieure de chimie de Paris · Institut Parisien de Chimie Moléculaire Sorbonne Université (research)

The synthesis and chemical oxidation profile of a new generation of ferrocifen derivatives with strong antiproliferative behavior in vitro is reported. In particular, the hydroxypropyl derivative HO(CH2 )3 C(Fc)=C(C6 H4 OH)2 (3 b) exhibited exceptional antiproliferative activity against the cancer cell lines HepG2 and MDA-MB-231 TNBC, with IC50 val...

We report here the synthesis and the strong and unexpected antiproliferative effect of the organometallic diphenolic compound 1,1-bis(4'-hydroxyphenyl)-2-ferrocenyl-but-1-ene (4) on both hormone-dependent (MCF7) and -independent (MDA-MB231) breast cancer cells (IC(50) = 0.7 and 0.6 microM). Surprisingly, 6 [1,2-bis(4'-hydroxyphenyl)-2-ferrocenyl-bu...

Herein we report the antiproliferative effects of a series of 28 compounds against the MDA-MB-231 breast cancer cell line, including the synthesis of seven new [3]ferrocenophanyl and four new ferrocenyl compounds. For each p-R-phenyl substitution pattern investigated, the [3]ferrocenophanyl derivatives were more cytotoxic than the corresponding fer...

A series of ruthenocene derivatives, 1-[4-(O(CH(2))(n)()N(CH(3))(2))phenyl]-1-(4-hydroxyphenyl)-2-ruthenocenylbut-1-ene, with n = 2-5, based on the structure of the breast cancer drug tamoxifen has been prepared. These compounds were obtained, via a McMurry cross-coupling reaction, as a mixture of Z and E isomers that could not be separated by HPLC...

Ferrociphenols (FCs) and their oxidized, electrophilic quinone methide metabolites (FC-QMs) are organometallic compounds related to tamoxifen that exhibit strong antiproliferative properties. To evaluate the reactivity of FC-QMs towards cellular nucleophiles, we studied their reaction with selected thiols. A series of new compounds resulting from t...

Ferroptosis has emerged as a form of programmed cell death and exhibits remarkable promise for anticancer therapy. However, it is challenging to discover ferroptosis inducers with new chemotypes and high ferroptosis-inducing potency. Herein, we report a new series of ferrocenyl-appended GPX4 inhibitors rationally designed in a “one stone kills two...

We sought to determine the cyclodextrins (CDs) best suited to solubilize a patented succinimido-ferrocidiphenol (SuccFerr), a compound from the ferrociphenol family having powerful anticancer activity but low water solubility. Phase solubility experiments and computational modelling were carried out on various CDs. For the latter, several CD-SuccFe...

Ferrocifens, lipophilic organometallic complexes, comprise a biologically active redox motif [ferrocenyl-ene-p-phenol] which confers very interesting cytotoxic properties to this family. However, because of their highly lipophilic nature, a formulation stage is required before being administered in vivo. In recent decades, ferrocifen lipid nanocaps...

The first fluorescent ferrociphenol derivative (P797) has been synthesized via McMurry cross-coupling followed by copper-catalyzed [3 + 2] azide-alkyne cycloaddition of the fluorescent group coumarin. Cyclic voltammograms of P797 exhibit either a monoelectronic oxidation wave ascribed to the ferrocene Fe(II) → Fe(III) conversion or a three-electron...

Ovarian cancer is one of the deadliest epithelial malignancies in women, owing to the multidrug resistance that restricts the success of conventional chemotherapy, carboplatin and paclitaxel. High grade serous ovarian carcinoma can be classified into two subtypes, the chemosensitive High OXPHOS and the Low OXPHOS tumour, less sensitive to chemother...

SuccFerr (N-[4-ferrocenyl,5-5-bis (4-hydroxyphenyl)-pent-4-enyl]-succinimide) has remarkable antiproliferative effects in vitro, attributed to the formation of a stabilized quinone methide. The present article reports in vivo results for a possible preclinical study. SuccFerr is lipophilic and insoluble in water, so the development of a formulation...

The [ferrocene-ene-phenol] motif has been identified as the pharmacophore responsible for the anticancer activity of the family of ferrocene-based molecules coined ferrocifens, owing to its unique redox properties. The addition of imide entities to the historical ferrociphenol scaffold tremendously enhanced the cytotoxic activity of a large panel o...

Ferrociphenols are characterized by the presence of a biologically active redox motif [ferrocenyl-ene-p-phenol], and are known to exhibit anticancer properties. Recent studies have identified a new series of ferrociphenols that bear an imido-type heterocycle at the terminus of a short alkyl chain, and which showed very strong antiproliferativity ag...

The family of ferrocifens initially built up from the anti‐oestrogen tamoxifen shows a broad antitumor activity both in vitro and in vivo. Their mechanism of action relies on the presence of the redox motif [ferrocene‐ene‐phenol] that, under oxidative conditions, generates reactive oxygen species (ROS) and affords electrophilic quinone methides (QM...

Glioblastoma (GBM) is the most frequent and deadliest primary brain cancer in adults, justifying the search for new treatments. Some members of the iron-based ferrocifen family have demonstrated a high cytotoxic effect on various cancer cell lines via innovative mechanisms of action. Here, we evaluated the antiproliferative activity by wst-1 assay...

Background Tamoxifen citrate is a very prevalent drug marketed under several trade names like Apo-Tamox, Nolvadex, Tamec, Tamizam and Tamoplex. This molecule is approved by the FDA for breast cancer treatment. Some studies have shown that tamoxifen has anti-tuberculosis and anti-parasitic activities. Like any drug tamoxifen possesses side effects,...

The design of simple platform in order to target the delivery of notably hydrophobic drugs into cancer cells is an ultimate goal. Here, three strategies were combined in a same nanovector, in limiting the use of excipients: a combination of cell-penetrating peptides (CPPs), amphiphilic prodrug and self-assembly. Light scattering and cryogenic trans...

The ferrocenyl diphenol complexes 1,1‐bis(4′‐hydroxyphenyl)‐2‐ferrocenyl‐but‐1‐ene (1) and 1,2‐bis(4′‐hydroxyphenyl)‐1‐ferrocenyl‐but‐1‐ene [(Z)‐2], which differ by the relative position of the two phenolic substituents, display dramatically different antiproliferative activities on cancer cells (1 is far more cytotoxic than 2). In this study, our...

Ferrociphenols, especially those possessing a heterocycle at the terminus of an aliphatic chain, display strong anticancer activity through a novel redox mechanism that generates active metabolites such as quinone methides (QMs). X‐ray crystallography and UV/Vis spectroscopy reveal that the specific lone pair (lp)–π interaction between a carbonyl g...

Ferrociphenols, especially those possessing a heterocycle at the terminus of an aliphatic chain, display strong anticancer activity via a novel redox mechanism that generates active metabolites such as quinone methides (QMs). X‐ray crystallography and UV‐Vis spectroscopy reveal that the specific lone pair (lp)‐π interaction between a carbonyl group...

The biodeterioration and blackening of vinyl glues before their expiration date of use was studied and shown to be of bacterial origin. Two bacterial isolates, responsible for this alteration were identified as sulfate-reducing bacteria. On the basis of biochemical properties and 16S rRNA gene sequencing, they were identified as Microbacterium oxyd...

Objective We synthesized new tamoxifen derivatives as anticancer drug candidates and elaborated on convection‐enhanced delivery (CED) as a strategy for delivery. Methods To overcome the issue of their poor solubility, these ferrocenyl‐tamoxifen derivatives were esterified and encapsulated into different nanocarriers, that is lipid (LNC) and polyme...

Increasing intracellular drug concentration using nanocarriers can be a potential strategy to improve efficacy against glioblastoma (GBM). Here, the fluorescent-labelled NFL-TBS.40-63 peptide (fluoNFL) concentration on lipid nanocapsule (LNC) was studied to enhance nanovector internalization into human GBM cells. The LNC surface-functionalization w...

Metals are cytotoxic and could be harmful to human health; however, as their effects are dose dependant, some of them could be used in chemotherapy. In the present work, mineral chromium (VI) showed that it is cytotoxic on both tumour (MCF-7, HeLa, Hep2 and Caco-2) and non-tumour (HEK293) cell lines. Interestingly, among seven complexes of arene tr...

Organometallic compounds bearing the redox motif [ferrocenyl-ene-phenol] have very promising antiproliferative properties which have been further improved by incorporating pertinent substituents able to engender new mechanisms. Here we show that novel ferrociphenols bearing a hydroxypropyl chain exhibit strong antiproliferative effects, in most cas...

Experimental part of the paper : "A new generation of ferrociphenols leads to a great diversity of reactive metabolites, and exhibits remarkable antiproliferative properties".

Ferrociphenols are known to display anticancer properties by original mechanisms dependent on redox properties and generation of active metabolites such as quinone methides. Recent studies have highlighted the positive impact of oxidative stress on chemosensitivity and prognosis of ovarian cancer patients. Ovarian adenocarcinomas are shown to be an...

Tamoxifen-like metallocifens (TLMs) of the group-8 metals (Fe, Ru, Os) show strong anti-proliferative activity on cancer cell lines resistant to apoptosis, owing to their unique redox properties. On the other hand, the thioredoxin system, which is involved in cellular redox balance, is often overexpressed in cancer cells, especially in tumour types...

Background & objective: The inhibitory effects of four series of aryl butene derivatives, active against breast cancer, on the monophenolase activity of tyrosinase, in melanin-free ink from Sepia officinalis, have been studied. Hydroxytamoxifen 1, ferrociphenol 17 and several aryl butene analogs have shown strong antiproliferative activity on horm...

As part of our ongoing study of the toxicity of compounds derived from 1,1-di(4-hydroxyphenyl)-2-ferrocenyl-but-1-ene, we recently showed that closely analogous [3]ferrocenophane complexes had an in vitro toxicity level substantially higher than that of their ferrocene counterparts, particularly in the case of mono- and diphenol complexes. In the c...

As previously reported, the ferrocenyl derivative HO(CH2)3C(Fc) = C(C6H4OH)2 (2) shows an excellent cytotoxic effect against MDA-MB-231 (TNBC) cancer cell lines. Building on an analysis of this molecular framework, a series of novel hydroxypropyl-ferrociphenol derivatives with modified terminal hydroxyl groups were synthesized, and their antiprolif...

This paper reports the inhibitory effect on the cytosolic thioredoxin reductase (TrxR1) in vitro by the ansa-ferrocifen derivative (ansa-FcdiOH, 1). We found that 1 decreased only slightly enzyme activity (IC50 = 8 μM), while 1*, the species generated by enzymatic oxidation by the HRP (horseradish peroxidase)/H2O2 mixture, strongly inhibited TrxR1...

In order to examine whether the length of the bridging chain in ansa-ferrocenes affects their antiproliferative activity against MDA-MB-231 triple negative breast cancer cell lines (TNBC), we synthesized derivatives of the type 1-[bis-(4-hydroxyphenyl)]methylidene-[n]ferrocenophane and 1-[(4-hydroxyphenyl)-phenyl]methylidene-[n]ferrocenophane with...

Ferrociphenols (FCs) and their oxidized, electrophilic quinone methide metabolites (FC-QMs) are organometallic compounds related to tamoxifen that exhibit strong antiproliferative properties. To evaluate the reactivity of FC-QMs toward cellular nucleophiles, we studied their reaction with selected thiols. A series of new compounds resulting from th...

Ferrociphenols (FCs) and their oxidized, electro-philic quinone methide metabolites (FC-QMs) are organo-metallic compounds related to tamoxifen that exhibit strong antiproliferative properties. To evaluate the reactivity of FC-QMs toward cellular nucleophiles, we studied their reaction with selected thiols. A series of new compounds resulting from...

Metabolischer Reigen: In ihrer Zuschrift (DOI: 10.1002/ange.201603931) berichten G. Jaouen und Mitarbeiter über die metabolische Aktivierung von Ferrociphenolen durch Lebermikrosome. Bei diesem Prozess entstehen Chinonmethide, die anschließend mit Thiolen, z. B. mit Glutathion, Addukte bilden. Das Verhalten dieser metallorganischen Addukte in einem...

The antiseptic and disinfectant potential of a formulation containing the tamoxifen analogue 1,1-bis[4-(3-dimethylaminopropoxy)phenyl]-2-ferrocenyl-but-1-ene citrate was assessed according to European standards and pharmacopeia in comparison with a commercial antiseptic product containing hexamidine diisethionate, chlorhexidine digluconate and chlo...

This work reports the in vitro activity against Plasmodium falciparumblood forms (W2 clone, chloroquine-resistant) of tamoxifen-based compounds and their ferrocenyl (ferrocifens) and ruthenocenyl (ruthenocifens) derivatives, as well as their cytotoxicity against HepG2 human hepatoma cells. Surprisingly with these series, results indicate that the b...

Several ferrocenyl analogues of tamoxifen have already showed strong antiproliferative activity in experimental glioma models. Nevertheless, these compounds are very poorly soluble in water and an adapted formulation is needed. In this work, we have tailored and optimized methylated cyclodextrin soluble complexes of phthalimido-ferrocidiphenol for...

(EN) The present invention relates to a compound of the following formula (I) or a pharmaceutically acceptable salt or solvate thereof, a stereoisomer or a mixture of stereoisomers in any ratio, or a water-soluble derivative, as well asto methods for preparing same and to the use thereof, in particular in the treatment of cancer. (FR) L'invention c...

Ferrociphenols have been found to have high antiproliferative activity against estrogen-independent breast cancer cells. The rat and human liver microsome-mediated metabolism of three compounds of the ferrocifen (FC) family, 1,1-bis(4-hydroxyphenyl)-2-ferrocenyl-but-1-ene (FC1), 1-(4-hydroxyphenyl)-1-(phenyl)-2-ferrocenyl-but-1-ene (FC2), and 1-[4-...

Many anticancer compounds are strong inhibitors of thioredoxin reductases (TrxRs), selenoenzymes involved in cellular redox regulation. This study examined the effect of two hydroxyferrocifens (1, FcOH; 2, FcOHTAM) and of their corresponding quinone methides (QMs), 1-QM, and 2-QM, on these enzymes. In vitro, both QMs were more potent TrxR inhibitor...

The aim of this work was to investigate the mechanism of action of 2-ferrocenyl-1,1-diphenylbut-1-ene (1) on HL-60 human leukemia cells. While inactive against noncancerous cells, 1 provoked a concentration-dependent decrease in viable tumor cells, primarily via apoptosis, as evidenced by analysis of cell morphology, activation of caspases 3 and 7,...

In the course of the preparation of a series of ferrocenyl derivatives of diethylstilbestrol (DES), in which one of the 4-hydroxyphenyl moieties was replaced by a ferrocenyl group, the McMurry reaction of chloropropionylferrocene with a number of mono-aryl ketones unexpectedly yielded the hydroxylated ferrocenyl DES derivatives, 5a-c, in poor yield...

The complete oxidation sequence of ruthenociphenol (1), an organometallic ruthenocenebased analogue of ferrocifens, a promising anticancer drug series, has been investigated by cyclic voltammetry. As for the unsubstituted ruthenocene, the oxidation of 1 produced the corresponding species 1+, which engaged in a reversible dimerization reaction. The...

The crown gall induced in potato discs by Agrobacterium tumefaciens is becoming largely utilised in screening anti-tumor agents. The present work is showing that beet discs are more adequate for the anti-tumor screening test. In fact, maximal tumor induction was observed on beet discs (87.5%), followed by carrot discs (75%) and potato discs (68.5%)...

In a previous work we have demonstrated the antimicrobial activity of ferrocenyl or phenyl derivatives of diphenyl butene series. This finding has opened a new area of applications of organometallic compounds. In order to improve these activities, we have synthesized new organic and organometallic diaryl butene compounds with different lengths of t...

Triple-negative breast cancers (TNBC) represent the most aggressive form of breast cancers and their treatment are challenging due to the tumor heterogeneity. The high death rate and the limited systemic treatment options for TNBC necessitate the search for alternative chemotherapeutics. We previously found that FcOHTAM, an organometallic derivativ...

With the aim of improving the cytotoxic and vascular disrupting activities of flavonoids, several classes of ferrocenyl-modified flavonoids were prepared and tested on cancer and endothelial cells. Three ten-member series of ferrocenyl flavonoids: chalcones ((E)-1-(R-2′-hydroxyphenyl)-3-ferrocenylprop-2-en-1-ones), aurones ((Z)-R-2-(ferrocenylidene...

We here report the synthesis and antiproliferative activities of two new series of ferrocenophanes obtained from McMurry cross-coupling reactions of [3]ferrocenophan-1-one with benzophenone, 4-hydroxybenzophenone, 4,4′-dihydroxybenzophenone, and 4,4′-diacetylaminobenzophenone. In addition to the main formation of olefins at reflux, tetrahedral tran...

The synthesis and anti-tumoral properties of a series of compounds possessing a ferrocenyl group tethered to a catechol via a conjugated system is presented. On MDA-MB-231 breast cancer cell lines, the catechol compounds display a similar or greater anti-proliferative potency (IC(50) values ranging from 0.48-1.21 μM) than their corresponding phenol...

La présente invention concerne, des composés chimiques citrates de diaryl butènes portant deux chaînes aminoalkyle. L’excellente efficacité antimicrobienne démontrée de ces composés [1], a été approfondie par l’essai du pouvoir antiseptique et désinfectant de l’un des produits de cette série et de son dérivé formulé. La confirmation du pouvoir anti...

Many plant pathogenic bacteria and fungi are known to infect olive trees, causing considerable crop losses. The present work deals with targeting some olive tree pathogens by ferrocene derivatives [1,1-bis-(4-hydroxyphenyl)- 2-ferrocenyl-but-1-ene] (P1); (Z+E)-1-(p-aminophenyl)- 1-phenyl-2-ferrocenyl-but-1-ene (P2); 2-ferrocenyl- 1-(4-N-acetylamino...

We have prepared several organometallic systems whose structures are closely analogous to that of tamoxifen, the drug used in the treatment of hormone-dependent breast cancers, but which now possess two basic aminoalkyl chains: O(CH2)3NMe2. Despite the absence of a phenolic functionality, these ferrocenyl compounds 3, 4 and their organic analogue 5...

Some ferrocene compounds, such as tamoxifen derivatives hydroxyferrocifen 1 and ferrociphenol 2, show strong antiproliferative activity on hormone-dependent and hormone-independent breast cancer cells. In order to evaluate their antimicrobial activity, they were tested, together with their purely organic analogs, on the bacteria Pseudomonas aerugin...

Les ferrocényl diaryl butènes ont démontré d’excellentes activités phytosanitaires contre diverses souches microbiennes connues pour leurs dégâts en olivier et arboriculture fruitière. Le présent brevet vise à protéger l’utilisation phytopharmaceutique de ces produits. En effet le « 1,1-bis[4-(3-Diméthylaminopropoxy)phényl]-2-ferrocényl-but-1-ène »...

N-Arylmethylphthalimidine-3-carboxylates 3 are good precursors for the synthesis of ketones 5a,b or enols 6c-e which upon acidic treatment led to lactones 7 via an N-acyliminium ion.

The synthesis of isoindolo[2,1‐ b ]pyrrolo[1,2‐ d ][2,4]benzodiazocine 7 and isoindolo[1,2‐ d ]pyrrolo[1,2‐ a ]‐[1,5]benzodiazocine 13 are described starting from 2‐(2‐methoxycarbonyl)benzylphthalimide 1a and ethyl α‐bromohomophthalate 9 respectively.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Cyclization of thioglycolic acids derivatives 3a-d gave isoindolo[l,2-b] thieno [2,3(3,2 or 3,4)-e][l,3]thiazocines 4a-d. Isoindolo[2,1-a] thieno [2,3(3,2 or 3,4)-f][l,4] or [l,5]diazocines 10b or 11a-c were synthesized from Beckmann or Schmidt rearrangement of the ketones 7a-c.

Isoindolo[2,1-b][2,4]benzodiazepines 11a-c were synthesized from hydroxylactam-acid 5 when it was treated successively with thionyl chloride, ammonia (or an alkylamine) and p-toluenesulfonic acid.

A series of new 1-[di-(4-R-phenyl)-methylidenyl)]-[3]ferrocenophanes, where R = OH, NH2, NHAc, and the phenyl substitution is mixed or identical, are highly antiproliferative against MDA-MB-231 and PC-3 cancer cells, with IC50 values ranging from 0.05–5.6 μM on MDA-MB-231 and 0.02–12.5 μM on PC-3.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The preparation of 3-carboxymethylamino (or oxy or thio)-2-aryl (or arylmethyl)-isoindol-1-ones are described from hydroxylactams according to three different pathways.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

N-alkyl isoindolo[2,l-b][2,4]benzodiazepines 15c were synthesized via an intramolecular N­acyliminium ion-amide reaction, N-aryl derivatives 8c were obtained from an intramolecular acylation of amino acids 6c in acetic anhydride. A generalization of these methodologies is given in the synthesis of the thiophenic analogues 15d and 8d.