Jean-Pierre Hénichart

Bio: Jean-Pierre Hénichart is an academic researcher from university of lille. The author has contributed to research in topics: Netropsin & Acylation. The author has an hindex of 29, co-authored 255 publications receiving 3570 citations. Previous affiliations of Jean-Pierre Hénichart include Lille University of Science and Technology & University of Notre Dame.

Anti-proliferative and apoptotic effects of anandamide in human prostatic cancer cell lines: implication of epidermal growth factor receptor down-regulation and ceramide production.

Abstract: BACKGROUND Anandamide (ANA) is an endogenous lipid which acts as a cannabinoid receptor ligand and with potent anticarcinogenic activity in several cancer cell types. METHODS The inhibitory effect of ANA on the epidermal growth factor receptor (EGFR) levels expressed on the EGF-stimulated prostatic cancer cells LNCaP, DU145, and PC3 was estimated by ELISA tests. The anti-proliferative and cytotoxic effects of ANA were also evaluated on these human prostatic cancer cell lines by growth tests, flow cytometric analyses, trypan blue dye exclusion assays combined with the Papanicolaou cytological staining method. RESULTS ANA induced a decrease of EGFR levels on LNCaP, DU145, and PC3 prostatic cancer cells by acting through cannabinoid CB1 receptor subtype and this leaded to an inhibition of the EGF-stimulated growth of these cells. Moreover, the G1 arrest of metastatic DU145 and PC3 growth was accompanied by a massive cell death by apoptosis and/or necrosis while LNCaP cells were less sensitive to cytotoxic effects of ANA. The apoptotic/necrotic responses induced by ANA on these prostatic cancer cells were also potentiated by the acidic ceramidase inhibitor, N-oleoylethanolamine and partially inhibited by the specific ceramide synthetase inhibitor, fumonisin B1 indicating that these cytotoxic actions of ANA might be induced via the cellular ceramide production. CONCLUSIONS The potent anti-proliferative and cytotoxic effects of ANA on metastatic prostatic cancer cells might provide basis for the design of new therapeutic agents for effective treatment of recurrent and invasive prostatic cancers. Prostate 56: 1–12, 2003. © 2003 Wiley-Liss, Inc.

Benzoselenazolinone derivatives designed to be glutathione peroxidase mimetics feature inhibition of cyclooxygenase/5-lipoxygenase pathways and anti-inflammatory activity.

Abstract: Two series of compounds, substituted benzoselenazolinones and their opened analogs, diselenides, were prepared. The diselenides were designed according to the available SAR about glutathione peroxidase mimics and were expected to have activity. An initial series of tests was performed in order to assess the glutathione peroxidase and antioxidant activity of the diselenides compared to their cyclized analogs. The diselenides were shown to be very potent (up to 3 times the activity of ebselen), whereas the benzoselenazolinones were inactive, thus confirming our hypothesis. A second series of tests was done to determine the anti-inflammatory potency of the two series. Both were found to be potent on cyclooxygenase and 5-lipoxygenase pathways (up to 95% inhibition at 10(-5) M). Some compounds were selective, and the variations in the activity allowed us to draft some structure-activity relationships. The most interesting compound of each series, 6-benzoylbenzoselenazolinone and bis[(2-amino-5-benzoyl)phenyl] diselenide, was tested in vivo on the rat foot edema induced with different phlogistic agents and was shown to have some anti-inflammatory properties.

The different binding modes of Hoechst 33258 to DNA studied by electric linear dichroism.

Abstract: The binding mode of the bisbenzimidazole derivative Hoechst 33258 to a series of DNAs and polynucleotides has been investigated by electric linear dichroism Positive reduced dichroisms were measured for the poly(dA-dT)poly(dA-dT)- and poly(dA)poly(dT)-Hoechst complexes in agreement with a deep penetration of the drug into the minor groove Similarly, the drug displays positive reduced dichroism in the presence of the DNAs from calf thymus, Clostridium perfringens and Coliphage T4 Conversely, negative reduced dichroisms were obtained when Hoechst 33258 was bound to poly(dG-dC)poly(dG-dC), poly(dA-dC)poly(dG-dT) and poly(dG)poly(dC) as well as with the GC-rich DNA from Micrococcus lysodeikticus indicating that in this case minor groove binding cannot occur Substitution of guanosines for inosines induces a reversal of the reduced dichroism from negative to positive Therefore, as anticipated it is the 2-amino group of guanines protruding in this groove which prevents Hoechst 33258 from getting access to the minor groove of GC sequences The ELD data obtained with the GC-rich biopolymers are consistent with an intercalative binding Competition experiments performed with the intercalating drug proflavine lend credence to the involvement of an intercalative binding rather than to an external or major groove binding of Hoechst 33258 at GC sequences

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

Abstract: The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson9s and Huntington9s disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment to the development of cannabinoid medications has been the socially unacceptable psychoactive properties of plant-derived or synthetic agonists, mediated by CB 1 receptors. However, this problem does not arise when the therapeutic aim is achieved by treatment with a CB 1 receptor antagonist, such as in obesity, and may also be absent when the action of endocannabinoids is enhanced indirectly through blocking their metabolism or transport. The use of selective CB 2 receptor agonists, which lack psychoactive properties, could represent another promising avenue for certain conditions. The abuse potential of plant-derived cannabinoids may also be limited through the use of preparations with controlled composition and the careful selection of dose and route of administration. The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients9 need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy.

Next Generation of Fluorine-Containing Pharmaceuticals, Compounds Currently in Phase II–III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas

Abstract: Compounds Currently in Phase II−III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas Yu Zhou,† Jiang Wang,† Zhanni Gu,† Shuni Wang,† Wei Zhu,† Jose ́ Luis Aceña,*,‡,§ Vadim A. Soloshonok,*,‡,∥ Kunisuke Izawa,* and Hong Liu*,† †Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China ‡Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizab́al 3, 20018 San Sebastiań, Spain Department of Organic Chemistry, Autońoma University of Madrid, Cantoblanco, 28049 Madrid, Spain IKERBASQUE, Basque Foundation for Science, María Díaz de Haro 3, 48013 Bilbao, Spain Hamari Chemicals Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka, Japan 533-0024

Organoselenium and Organotellurium Compounds: Toxicology and Pharmacology

Abstract: The organoselenium and organotellurium compounds have been described as promising pharmacological agents in view of their unique biological properties. Glutathione peroxidase mimic, antioxidant activity and thioredoxin reductase inhibition are some of the properties reviewed here. On the other hand, little is known about the molecular toxicological effects of organoselenium and organotellurium compounds. Most of our knowledge arose from research on inorganic selenium and tellurium. However, the ability to oxidize sulfhydryl groups from biological molecules can be involved both in their pharmacological properties and in their toxicological effects. In fact, exposition to high doses of organoselenium or to low doses of organotellurium causes the depletion of endogenous reduced glutathione in a variety of tissues. Thus, the design of compounds that cause low depletion of glutathione and react with specific targeted proteins, controlling specific metabolic pathways, will represent an important progress in understanding the field of organochalcogen compounds. Furthermore, the development of new organochalcogens with higher thiol-peroxidase activity that can use other non-toxic thiol reducing agents, such as N-acetylcysteine instead of glutathione, will permit the investigation of the co-administration of organochalcogens and thiols as a formulation for antioxidant therapy.