Abdelaziz Ejjoummany
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Abdelaziz Ejjoummany has a total of 10 co-authors. Here are the top co-authors by number of shared publications:
- Anne-Dominique Lajoix
Biocommunication in Cardio-Metabolism (BC2M), University of Montpellier, 34093 Montpellier, France
1 shared publication - Booma Ramassamy
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR 8601, CNRS, Université Paris Descartes, CEDEX 06, 75270 Paris, France
1 shared publication - Elodie Mauchauffée
Institut des Biomolécules Max Mousseron, CNRS, Univ. Montpellier, ENSCM, Pôle Chimie Balard, 34293 Montpellier, France
1 shared publication - Jean-François Hernandez
IBMM, CNRS, Univ Montpellier, ENSCM, Montpellier, France
1 shared publication - Jean-Luc Boucher
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR 8601, CNRS, Université Paris Descartes, CEDEX 06, 75270 Paris, France
1 shared publication - Jihanne Chamcham
Institut des Biomolécules Max Mousseron, CNRS, Univ. Montpellier, ENSCM, Pôle Chimie Balard, 34293 Montpellier, France
1 shared publication
Latest Publications
- Open Access
S-Ethyl-Isothiocitrullin-Based Dipeptides and 1,2,4-Oxadiazole Pseudo-Dipeptides: Solid Phase Synthesis and Evaluation as NO Synthase Inhibitors
We previously reported dipeptidomimetic compounds as inhibitors of neuronal and/or inducible NO synthases (n/iNOS) with significant selectivity against endothelial NOS (eNOS). They were composed of an S-ethylisothiocitrullin-like moiety linked to an extension through a peptide bond or a 1,2,4-oxadiazole link. Here, we developed two further series where the extension size was increased to establish more favorable interactions in the NOS substrate access channel. The extension was introduced on the solid phase by the reductive alkylation of an amino-piperidine moiety or an aminoethyl segment in the case of dipeptide-like and 1,2,4-oxadiazole compounds, respectively, with various benzaldehydes. Compared to the previous series, more potent inhibitors were identified with IC50 in the micromolar to the submicromolar range, with significant selectivity toward nNOS. As expected, most compounds did not inhibit eNOS, and molecular modeling was carried out to characterize the reasons for the selectivity toward nNOS over eNOS. Spectral studies showed that compounds were interacting at the heme active site. Finally, selected inhibitors were found to inhibit intra-cellular iNOS and nNOS expressed in RAW264.7 and INS-1 cells, respectively.
Open AccessS-Ethyl-Isothiocitrullin-Based Dipeptides and 1,2,4-Oxadiazole Pseudo-Dipeptides: Solid Phase Synthesis and Evaluation as NO Synthase Inhibitors
We previously reported dipeptidomimetic compounds as inhibitors of neuronal and/or inducible NO synthases (n/iNOS) with significant selectivity against endothelial NOS (eNOS). They were composed of an S-ethylisothiocitrullin-like moiety linked to an extension through a peptide bond or a 1,2,4-oxadiazole link. Here, we developed two further series where the extension size was increased to establish more favorable interactions in the NOS substrate access channel. The extension was introduced on the solid phase by the reductive alkylation of an amino-piperidine moiety or an aminoethyl segment in the case of dipeptide-like and 1,2,4-oxadiazole compounds, respectively, with various benzaldehydes. Compared to the previous series, more potent inhibitors were identified with IC50 in the micromolar to the submicromolar range, with significant selectivity toward nNOS. As expected, most compounds did not inhibit eNOS, and molecular modeling was carried out to characterize the reasons for the selectivity toward nNOS over eNOS. Spectral studies showed that compounds were interacting at the heme active site. Finally, selected inhibitors were found to inhibit intra-cellular iNOS and nNOS expressed in RAW264.7 and INS-1 cells, respectively.