References of "Pirotte, Bernard"
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See detailPotential of caffeic acid derivatives as antimalarial leads.
Degotte, Gilles ULiege; Pirotte, Bernard ULiege; Francotte, Pierre ULiege et al

in Letters in Drug Design and Discovery (in press)

Malaria remains one of the deadliest infectious disease in 2021. Indeed, this infection, mostly caused by a protozoon called Plasmodium falciparum, is responsible annually for more than 200 million cases ... [more ▼]

Malaria remains one of the deadliest infectious disease in 2021. Indeed, this infection, mostly caused by a protozoon called Plasmodium falciparum, is responsible annually for more than 200 million cases and around 400 000 related deaths, mainly in Africa. Despite the availability of efficient drugs, we observe an increase of patients since 2015, which could find its origin in development of resistances from the parasite but also from its vectors, Anopheles mosquitoes. Consequently, it is necessary to search for new alternative treatments. Polyphenols, and more precisely small phenolic acids, could represent a good starting point for new antimalarials. Indeed, these molecules, such as caffeic acid (1), exhibit several pharmacological activities and an interesting pharmacokinetic profile. Therefore, we have developed several small derivatives of this scaffold to define the potential pharmacophore responsible for the antiplasmodial properties. We have obtained a good to low activity on Plasmodium (IC50 = 16-241 µM) with selectivity against human cells, especially for small esters (2-6, SI > 3). These structures have highlighted the need of catechol and carboxyl moieties in the anti-Plasmodium effect. Unfortunately, none of them seemed sufficiently effective to become a new antimalarial, but they could be new leads for future development. [less ▲]

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See detailDevelopment of Thiochroman Dioxide Analogues of Benzothiadiazine Dioxides as New Positive Allosteric Modulators of α-Amino-3- hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors
Etse, Koffi Senam ULiege; Dorosz, Jerzy; Mc Lain Christensen et al

in ACS Chemical Neurosciences (in press)

Based on the activity of 1,2,4-benzothiadiazine 1,1-dioxides as AMPAR-PAMs, thiochroman 1,1-dioxides were designed apply- ing the isosteric replacement concept. The new compounds expressed a strong ... [more ▼]

Based on the activity of 1,2,4-benzothiadiazine 1,1-dioxides as AMPAR-PAMs, thiochroman 1,1-dioxides were designed apply- ing the isosteric replacement concept. The new compounds expressed a strong modulatory activity on AMPARs in vitro, although lower than their corresponding benzothiadiazine analogues. The pharmacokinetic profile of three thiochroman 1,1-dioxides (12a, 12b, 12e) was exam- ined in vivo after oral administration, showing that these compounds freely cross the blood-brain barrier. Structural analysis was achieved using X-ray crystallography after cocrystallisation of the racemic compound 12b in complex with GluA2-LBD (L504Y/N775S). Interestingly, both enantiomers of 12b were found to interact with the GluA2-LBD dimer interface, almost identically to its benzothiadiazine analogue, BPAM344 (4). The interactions of the two enantiomers in the cocrystal were further analyzed (mapping Hirshfeld surfaces and 2D finger- print) and compared to those of 4. Taken together, these data explain the lower affinity on AMPARs of thiochroman 1,1-dioxides compared to their corresponding 1,2,4-benzothiadiazine 1,1-dioxides. [less ▲]

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See detailDeciphering the role of the GPR101 orphan receptor in growth hormone hypersecretion
Abboud, Dayana ULiege; Daly, Adrian ULiege; Dupuis, Nadine et al

Poster (2022, April)

Detailed reference viewed: 25 (1 ULiège)
See detailDeciphering the role of the GPR101 orphan receptor in growth hormone hypersecretion
Abboud, Dayana ULiege; Daly, Adrian ULiege; Dupuis, Nadine et al

Conference (2022, February)

Detailed reference viewed: 20 (1 ULiège)
See detailDeciphering the role of the GPR101 orphan receptor in growth hormone hypersecretion
Abboud, Dayana ULiege; Daly, Adrian ULiege; Dupuis, Nadine et al

Poster (2021, October)

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH secreting pituitary tumors over ... [more ▼]

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH secreting pituitary tumors over-expressing the orphan G-protein coupled receptor, GPR101(Trivellin et al, 2014). The role of GPR101 in GH secretion remains obscure. We studied GPR101 signaling pathways and their effects in HEK293 and rat pituitary GH3 cell lines, human tumors and in transgenic mice with elevated somatotrope Gpr101 expression driven by the rat Ghrhr promoter (GhrhrGpr101). We reported that Gpr101 causes elevated GH/prolactin secretion in transgenic GhrhrGpr101 mice but without hyperplasia/tumorigenesis (Abboud et al, 2020). Furthermore, we showed that GPR101 constitutively activates not only Gs, but also Gq/11 and G12/13, which leads to GH secretion but not proliferation. These signatures of GPR101 signaling, notably PKC activation, are also present in human pituitary tumors with high GPR101 expression. These results underline a role for GPR101 in the regulation of somatotrope axis function. [less ▲]

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See detailPolyhydroxybenzoic acid derivatives as potential new antimalarial agents
Degotte, Gilles ULiege; Pirotte, Bernard ULiege; Frederich, Michel ULiege et al

in Archiv der Pharmazie und Berichte der Deutschen Pharmazeutischen Gesellschaft (2021)

With more than 200 million cases and 400,000 related deaths, malaria remains one of the deadliest infectious diseases of 2021. Unfortunately, despite the availability of efficient treatments, we have ... [more ▼]

With more than 200 million cases and 400,000 related deaths, malaria remains one of the deadliest infectious diseases of 2021. Unfortunately, despite the availability of efficient treatments, we have observed an increase in people infected with malaria since 2015 (from 211 million in 2015 to 229 million in 2019). This trend could partially be due to the development of resistance to all the current drugs. Therefore, there is an urgent need for new alternatives. We have, thus, selected common natural scaffolds, polyhydroxybenzoic acids, and synthesized a library of derivatives to better under- stand the structure–activity relationships explaining their antiplasmodial effect. Only gallic acid derivatives showed a noticeable potential for furtherQ3 developments. Indeed, they showed a selective inhibitory effect on Plasmodium (IC50 ~20 μM, SI > 5) often associated with interesting water solubility. Moreover, this has confirmed the critical importance of free phenolic functions (pyrogallol moiety) for the antimalarial effect. Methyl 4-benzoxy-3,5-dihydroxybenzoate (39) has, for the first time, been recognized as a potential lead for future research because of its marked inhibitory activity against Plasmodium falciparum and its significant hydrosolubility (3.72 mM). [less ▲]

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See detailGPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11
Abboud, Dayana ULiege; Daly, Adrian ULiege; Dupuis, Nadine et al

Conference (2021, April)

Detailed reference viewed: 16 (1 ULiège)
See detailGPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11
Abboud, Dayana ULiege; Daly, Adrian ULiege; Dupuis, Nadine et al

Conference (2021, April)

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See detailOverview of natural antiplasmodials from the last decade to inspire medicinal chemistry
Degotte, Gilles ULiege; Pirotte, Bernard ULiege; Francotte, Pierre ULiege et al

in Current Medicinal Chemistry (2021)

Background: Despite the major advances in the fight against this parasitic disease, malaria remains a major cause of concerns in 2020. This infection, mainly due to Plasmodium falciparum, causes every ... [more ▼]

Background: Despite the major advances in the fight against this parasitic disease, malaria remains a major cause of concerns in 2020. This infection, mainly due to Plasmodium falciparum, causes every year more than 200 million of cases and hundreds of thousands of deaths in developing regions, mostly in Africa. The last statistics show an increase of cases for the third consecutive year, from 211 million in 2015, it has reached 229 million in 2019. This trend could be partially explained by the appearance of resistances to all the used antimalarials, even to artemisinin. Thus, the design of new anti-Plasmodium compounds is an urgent need. For thousands of years, nature has offered to humans the medicines to cure their diseases or the inspiration for development of new active principles. It seems then logical to explore the natural sources to find new molecules to treat this parasitosis. Method: Therefore, this review reports and analyzes the extracts (plants, bacteria, sponges, fungi) and the corresponding isolated compounds showing antiplasmodial properties between 2013 and 2019. Results & Conclusion: Nature remains a major source of active compounds. Indeed, 648 molecules from various origins, mostly plants, have been reported for their inhibitory effect on Plasmodium falciparum. Among them, 188 scaffolds were defined as highly active with IC50 ≤ 5 µM and have been reported here in details. Moreover, the most active compounds showed a large variety of structures: flavonoids, triterpenes, alkaloids... Therefore, these compounds could be an interesting source of inspiration for medicinal chemists. May-be several of these molecules should become the next leads for malaria treatment. [less ▲]

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See detailGPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11
Abboud, Dayana ULiege; Daly, Adrian ULiege; Dupuis, Nadine et al

Conference (2020, November)

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See detailGPR101 drives growth hormone hypersecretion and gigantism in mice via constitutive activation of Gs and Gq/11
Abboud, Dayana ULiege; Daly, Adrian ULiege; Dupuis, Nadine ULiege et al

in Nature Communications (2020), 11(1), 4752

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH-secreting pituitary tumors over ... [more ▼]

Growth hormone (GH) is a key modulator of growth and GH over-secretion can lead to gigantism. One form is X-linked acrogigantism (X-LAG), in which infants develop GH-secreting pituitary tumors over-expressing the orphan G-protein coupled receptor, GPR101. The role of GPR101 in GH secretion remains obscure. We studied GPR101 signaling pathways and their effects in HEK293 and rat pituitary GH3 cell lines, human tumors and in transgenic mice with elevated somatotrope Gpr101 expression driven by the rat Ghrhr promoter (GhrhrGpr101). Here, we report that Gpr101 causes elevated GH/prolactin secretion in transgenic GhrhrGpr101 mice but without hyperplasia/tumorigenesis. We show that GPR101 constitutively activates not only Gs, but also Gq/11 and G12/13, which leads to GH secretion but not proliferation. These signatures of GPR101 signaling, notably PKC activation, are also present in human pituitary tumors with high GPR101 expression. These results underline a role for GPR101 in the regulation of somatotrope axis function. [less ▲]

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See detailSynthesis, crystal structure, Hirshfeld surface and interaction energies analysis of 5-methyl-1,3-bis(3-nitrobenzyl)pyrimidine-2,4(1H,3H)-dione
Etse, Koffi Senam ULiege; Comeron Lamela, Laura ULiege; Zaragoza, Guillermo et al

in European Journal of Chemistry (2020), 11/2

The title compound 5-methyl-1,3-bis(3-nitrobenzyl)pyrimidine-2,4(1H,3H)-dione was obtained by reaction of thymine with 3-nitrobenzylbromide in the presence of cesium carbonate. Characterization of the ... [more ▼]

The title compound 5-methyl-1,3-bis(3-nitrobenzyl)pyrimidine-2,4(1H,3H)-dione was obtained by reaction of thymine with 3-nitrobenzylbromide in the presence of cesium carbonate. Characterization of the product was achieved by NMR spectroscopy and its stability was probed in basic condition using UV-Visible analysis. Furthermore, the molecular structure was confirmed by X-ray diffraction analysis. The compound crystallizes in orthorhombic Pna21 space group with unit cell parameters a = 14.9594 (15) Å, b = 25.711 (3) Å, c = 4.5004 (4) Å, V = 1731.0 (3) Å3 and Z = 4. The crystal packing of the title compound is stabilized by intermolecular hydrogen bond, π···π and C−H···π stacking interactions. The intermolecular interactions were furthermore analyzed through the mapping of different Hirshfeld surfaces. The two-dimensional fingerprint revealed that the most important contributions to these surfaces come from O···H (37.1%), H···H (24%) and H···C/C···H (22.6%) interactions. The interaction energies stabilizing the crystal packing were calculated and were presented graphically as framework energy diagrams. Finally, the energy-framework analysis reveals that π···π and C−H···π interactions energies are mainly dispersive and are the most important forces in the crystal. [less ▲]

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