title: Search for novel neuraminidase inhibitors: Design, synthesis and interaction of oseltamivir derivatives with model membrane using docking, NMR and DSC methods.
abstract: As a part of our ongoing program of developing novel influenza virus inhibitors, some new derivatives of oseltamivir were prepared by modifying the amino group with glycyl, acetyl, benzyl and prolyl moieties. The interactions of these derivatives with neuraminidase have been probed by molecular modeling techniques. Further, the interaction of these derivatives with model membranes prepared from DPPC and the effect on the thermotropic behavior and polymorphism of the bilayers have been investigated by multinuclear NMR and DSC methods. Results indicate that the glycyl derivative of oseltamivir has the most profound effects on the membrane, compared to other derivatives and seems to be the most promising derivative for further pharmacological evaluation as a neuraminidase inhibitor.
authors.affiliation: Prin K M Kundnani College of Pharmacy, Cuffe Parade, Mumbai-400005, India.
authors.forename: Charlotte
authors.initials: C
authors.lastname: D'Souza
authors.forename: Meena
authors.initials: M
authors.lastname: Kanyalkar
authors.forename: Mamata
authors.initials: M
authors.lastname: Joshi
authors.forename: Evans
authors.initials: E
authors.lastname: Coutinho
authors.forename: Sudha
authors.initials: S
authors.lastname: Srivastava
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000998:Antiviral Agents / Q000138:chemical synthesis*; D002152:Calorimetry, Differential Scanning; D020134:Catalytic Domain; D003198:Computer Simulation; D015195:Drug Design; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects*; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D019906:Nuclear Magnetic Resonance, Biomolecular; D053139:Oseltamivir / Q000031:analogs & derivatives* / Q000138:chemical synthesis
chemical_list: D000998:Antiviral Agents; D008051:Lipid Bilayers; D008081:Liposomes; D053139:Oseltamivir; D015060:1,2-Dipalmitoylphosphatidylcholine; D009439:Neuraminidase