Henri Bocquillon-Limousin (1856-1917). Un pharmacien passionné par la matière médicale

Henri Bocquillon-Limousin (1856-1917) -A pharmacist fascinated by materia medica – Henri Bocquillon-Limousin (1856-1917) get married with the daughter of Stanislas Limousin in 1885. After being graduated from pharmacy high school of Paris, he joined the laboratory of Jungfleisch. Afterwards, he briefly worked in the municipal laboratory of Paris and then he turned to a pharmacy activity. He took up the pharmacy of his father in law in 1887. His research was mainly directed to materia medica and valorization of colonial medicinal plants. Thanks to a well expanded network of associates, he managed to obtain an important collection of medicinal plants which is actually preserved in “François Tillequin museum – Collections of materia medica” in the faculty of pharmacy of Paris. H. Bocquillon-Limousin is also well known for his numerous editions of Formulaire des médicaments nouveaux and his books in the field of material medica.Henri Bocquillon-Limousin (1856-1917) épouse la fille de Stanislas Limousin en 1885. Après avoir été diplômé de l’École supérieure de pharmacie de Paris, il intègre le laboratoire de Jungfleisch puis il s’oriente vers l’officine après un bref passage par le laboratoire municipal de Paris. Il reprend l’officine de son beau-père en 1887. Ses travaux de recherches sont essentiellement orientés vers la matière médicale et la valorisation des plantes médicinales des colonies. Grâce à un réseau de collaborateurs bien développé, il crée une importante collection de plantes médicinales qui est aujourd’hui conservée dans le musée François Tillequin-Collections de matières médicale de la Faculté de pharmacie de Paris. H. Bocquillon-Limousin est également reconnu pour les nombreuses éditions de son Formulaire des médicaments nouveaux et ses écrits en matière médicale.Gaslonde Thomas, Corlay Nina. Henri Bocquillon-Limousin (1856-1917). Un pharmacien passionné par la matière médicale. In: Revue d'histoire de la pharmacie, 103e année, N. 390, 2016. pp. 241-248

Structure, synthèse et activité biologique d'analogues structuraux, de dimères et de métabolites potentiels en séries acronycine, benzo[a]acronycine et benzo[b]acronycine

Le S23906-1, est un antitumoral dérivé de l acronycine. La configuration absolue de chacun des deux énantiomères du S23906-1 est déterminée. L énantiomère (1S,2S) a une activité antitumorale supérieure à celle du racémique et de l énantiomère (1R,2R). En vue de l obtention de composés aussi actifs que le S23906-1 mais possédant une solubilité accrue dans les solvants biocompatibles, des produits substitués en position 10 par une amine ou un alcool ont été préparés. Ils ont été synthétisés en utilisant la 10-bromobenzo[a]acronycine et de la 10-bromobenzo[b]acronycine comme intermédiaires. Les 10-hydroxybenzoacronycines obtenues sont des métabolites potentiels des benzoacronycines correspondantes. Le S23906-1 alkyle les positions 2 des unités guanines de l ADN. Afin d obtenir des bisalkylants, des dimères constitués de deux unités benzo[b]acronycine reliées par une chaîne a- -alkyldiéther ainsi que des dimères de type base de Tröger ont été synthétisés.S23906-1 is an antitumor agent derived from acronycine. The absolute configuration of S23906-1 enantiomers has been established. The (1S,2S) enantiomer displays a better antitumor activity than the racemic and the (1R,2R) enantiomer. In order to obtain compounds as active as S23906-1 but with a better solubility in biocompatible solvents, products substituted at position 10 by an amino or a hydroxy group have been prepared. These compounds have been synthetized using 10-bromobenzo[a]acronycine and 10-bromobenzo[b]acronycine as intermediates. Furthermore 10-hydroxybenzoacronycines are potential metabolites of the corresponding benzoacronycines. S23906-1 alkylates the position 2 of DNA guanine units. In order to obtain bisalkylating agents, dimers constituted by two benzo[b]acronycine units linked by a a- -alkyldiether chain or Tröger s base dimers have been synthetizedPARIS-BIUP (751062107) / SudocSudocFranceF

Origines et émergence de l’American Way of Pharmacy

Origin and appearance of American Way of Pharmacy – The American Way of Pharmacy is often characterized by its attachment to the Liberty principle, so dear to the Americans. But the practice of Pharmacy in North America is written in a long sequence of events, which begin with the first Amerindian tribes. The discovery of the New World induced a so rapid colonization that its society couldn’t organize the medicinal drugs’ market the same way it was in Europe. While explorers and botanists were amazed by the local pharmacopeia, small traders and shop owners had to step in and cover the needs on the whole territory. And it is only with the creation of the College of Philadelphia in 1821, that these new pharmacists decided to organize themselves in associations, to control decent formation and access to the profession. Finally, this pivotal period is well-documented enough, and the analysis of the structuration of Pharmacy in parallel to the Independency of the United States of America and Canada, gives a new insight to the modern and pharmaceutical society.L’American Way of Pharmacy est souvent caractérisé par un attachement très particulier au principe de Liberté si cher aux Américains. Mais la pratique de la pharmacie en Amérique du Nord s’inscrit dans une longue séquence d’événements qui démarrent dès l’époque des premières tribus amérindiennes. La découverte du nouveau continent a entrainé une colonisation trop rapide pour que la société structure le marché des médicaments, tel que déjà fonctionnel en Europe. Pendant que la pharmacopée locale émerveillait explorateurs et botanistes, l’implication de simples commerçants a permis de couvrir les besoins sur l’ensemble du territoire. Et c’est seulement avec la mise en place du Collège de Philadelphie en 1821, que les nouveaux professionnels en pharmacie ont commencé à s’organiser en associations, dans l’objectif de contrôler la formation et l’accès au métier. Cette période charnière est finalement bien documentée, et l’analyse de la structuration de la profession en parallèle à l’obtention d’indépendance des États-Unis et du Canada, donne un nouvel éclairage à la société pharmaceutique des temps modernes.Saxce Marguerite de, Gaslonde Thomas. Origines et émergence de l’American Way of Pharmacy. In: Revue d'histoire de la pharmacie, 106e année, N. 403, 2019. pp. 399-412

Progress on PPAPs cyclization: Guttiferone A as a case study

International audienc

Spirokermeline: A Macrocyclic Spirolactone from Kermadecia elliptica Brongn. & Gris

Spirokermeline, a new macrocyclic compound derived from resorcinol, was isolated from Kermadecia elliptica, an endemic species of New Caledonia. The structure of spirokermeline was elucidated on the basis of spectroscopic analysis and X-ray single-crystal diffraction analysis. This is the first time that a 3H,3′H-spiro[benzofuran-2,1′-isobenzofuran]-3,3′-dione was isolated from higher plants and only the second time that this scaffold was found in nature. A possible biosynthetic pathway is proposed

Functional characterization of the GATA-type transcription factor PaNsdD in the filamentous fungus Podospora anserina and its interplay with the sterigmatocystin pathway

International audienceThe model ascomycete Podospora anserina, featured by its strict sexual development, is a prolific but yet unexploited reservoir of natural products. The GATA-type transcription factor NsdD has been characterized by the role in balancing asexual and sexual reproduction, and governing secondary metabolism in filamentous fungi. In the present study, we functionally investigated the NsdD ortholog PaNsdD in P. anserina. Compared to the wild-type strain, vegetative growth, ageing processes, sexual reproduction, stress tolerance and interspecific confrontations in the mutant were drastically impaired, owing to the loss of function of PaNsdD. In addition, the production of 3-acetyl-4-methylpyrrole, a new metabolite identified in P. anserina in this study, was significantly inhibited in the ΔPaNsdD mutant. We also demonstrated the interplay of PaNsdD with the sterigmatocystin biosynthetic gene pathway, especially as the deletion of PaNsdD triggered the enhanced red-pink pigment biosynthesis that only occurs in the presence of the core polyketide synthase-encoding gene PaStcA of the sterigmatocystin pathway. Taken together, these results contribute to a better understanding of the global regulation mediated by PaNsdD in P. anserina, especially with regard to its unexpected involvement in fungal ageing process and its interplay with sterigmatocystin pathway. Importance Fungal transcription factors play an essential role in coordinating multiple physiological processes. Yet, little is known about the functional characterization of transcription factors in the filamentous fungus P. anserina. In this study, a GATA-type regulator PaNsdD was investigated in P. anserina. The results showed that PaNsdD was a key factor that can control the fungal ageing process, vegetative growth, pigmentation, stress response, interspecific confrontations, and positively regulate the production of 3-acetyl-4-methylpyrrole. Meanwhile, a molecular interaction was implied between PaNsdD and the sterigmatocystin pathway. Overall, loss of function of PaNsdD seems to be highly disadvantageous for P. anserina, which relies on pure sexual reproduction in limited lifespan. Therefore, PaNsdD is clearly indispensable for the survival and propagation of P. anserina in its complex ecological niches

Complementary Strategies to Unlock Biosynthesis Gene Clusters Encoding Secondary Metabolites in the Filamentous Fungus <i>Podospora anserina</i>

The coprophilous ascomycete Podospora anserina is known to have a high potential to synthesize a wide array of secondary metabolites (SMs). However, to date, the characterization of SMs in this species, as in other filamentous fungal species, is far less than expected by the functional prediction through genome mining, likely due to the inactivity of most SMs biosynthesis gene clusters (BGCs) under standard conditions. In this work, our main objective was to compare the global strategies usually used to deregulate SM gene clusters in P. anserina, including the variation of culture conditions and the modification of the chromatin state either by genetic manipulation or by chemical treatment, and to show the complementarity of the approaches between them. In this way, we showed that the metabolomics-driven comparative analysis unveils the unexpected diversity of metabolic changes in P. anserina and that the integrated strategies have a mutual complementary effect on the expression of the fungal metabolome. Then, our results demonstrate that metabolite production is significantly influenced by varied cultivation states and epigenetic modifications. We believe that the strategy described in this study will facilitate the discovery of fungal metabolites of interest and will improve the ability to prioritize the production of specific fungal SMs with an optimized treatment

Complementary Strategies to Unlock Biosynthesis Gene Clusters Encoding Secondary Metabolites in the Filamentous Fungus Podospora anserina

International audienceThe coprophilous ascomycete Podospora anserina is known to have a high potential to synthesize a wide array of secondary metabolites (SMs). However, to date, the characterization of SMs in this species, as in other filamentous fungal species, is far less than expected by the functional prediction through genome mining, likely due to the inactivity of most SMs biosynthesis gene clusters (BGCs) under standard conditions. In this work, our main objective was to compare the global strategies usually used to deregulate SM gene clusters in P. anserina, including the variation of culture conditions and the modification of the chromatin state either by genetic manipulation or by chemical treatment, and to show the complementarity of the approaches between them. In this way, we showed that the metabolomics-driven comparative analysis unveils the unexpected diversity of metabolic changes in P. anserina and that the integrated strategies have a mutual complementary effect on the expression of the fungal metabolome. Then, our results demonstrate that metabolite production is significantly influenced by varied cultivation states and epigenetic modifications. We believe that the strategy described in this study will facilitate the discovery of fungal metabolites of interest and will improve the ability to prioritize the production of specific fungal SMs with an optimized treatment

Identification de deux phytostérols biologiquement actifs de l’extrait cyclohexanique des feuilles de <i>Ficus sur</i> (Moraceae)

Ficus sur est une plante alimentaire couramment utilisée en médecine traditionnelle au Togo. Elle a cependant fait l’objet de très peu d’études phytochimiques. Le présent travail a pour but de valoriser cette espèce à travers l’identification continue de ses métabolites. Ainsi, l’extraction cyclohexanique au Soxhlet a été réalisée sur les feuilles de Ficus sur. Cet extrait cyclohexanique obtenu a été ensuite fractionné puis purifié par chromatographie sur colonne de gel de silice. L’identification des composés a été réalisée par GC-MS, précédée quelquefois d’une étape de dérivatisation. Treize fractions (A1 à A13) ont été obtenues du fractionnement de cet extrait. Après deux purifications successives de la fraction A5, deux sous-fractions A5.1 et A5.2 ont été obtenues. Le spectre de masse d’un composé de A2 présente un pic moléculaire à m/z 426 et des pics fragments [M-69]+, [M-154]+, [M-169]+, [M-197]+, [M-208]+ et [M-219]+ caractéristique du taraxastérol. Pour A5.2 dérivatisée, un composé présente un spectre de masse de pic moléculaire à m/z 486 et des pics fragments [M-90]+, [M-129]+ et [M-357]+ propres au β-sitostérol triméthylsilyl éther dérivé du β-sitostérol. La présence de ces deux phytostérols bioactifs serait un atout majeur dans l’usage thérapeutique de cette plante.© 2017 International Formulae Group. All rights reserved.Mots clés: Ficus sur, GC-MS, taraxastérol, β-sitostérolEnglish Title: Identification of two bioactive phytosterols of the cyclohexane extract of Ficus sur (moraceae) leavesEnglish AbstractFicus sur is a food plant commonly used in traditional medicine in Togo. However, few phytochemical studies of this species are available. This work aims at contributing to the enhancement of this approach through an identification of its metabolites. The leaves of Ficus sur were then extracted with cyclohexane using soxhlet. The obtained cyclohexane extract was fractionated and purified by chromatography on silica gel column. Identification of the compounds was carried out by GC-MS, sometimes preceded by a derivatization step. Thirteen fractions (A1 to A13) were obtained from the fractionation of this extract. After two successive purifications of the fraction A5, two subfractions A5.1 and A5.2 were obtained. The mass spectrum of a compound of A2 has a molecular peak at m/z 426 and peaks [M-69]+, [M-154]+, [M-169]+, [M-197]+, [M-208]+ and [M-219]+ characteristic of taraxasterol. For the derivatized fraction A5.2, a compound has a mass spectrum of molecular peak at m/z 486 and peaks [M-90]++ and [M-357]+ characteristic of β-sitosterol trimethylsilyl ether derived from β-sitosterol. The presence of these two bioactive phytosterols would be a major asset in the therapeutic use of this plant.© 2017 International Formulae Group. All rights reserved.Keywords: Ficus sur, GC-MS, taraxasterol, β-sitostero