title: Interactions of the potent synthetic AT1 antagonist analog BV6 with membrane bilayers and mesoporous silicate matrices.
abstract: The present work describes the drug:membrane interactions and a drug delivery system of the novel potent AT1 blocker BV6. This designed analog has most of the pharmacological segments of losartan and an additional biphenyltetrazole moiety resulting in increased lipophilicity. We found that BV6:membrane interactions lead to compact bilayers that may in part explain its higher in vitro activity compared to losartan since such environment may facilitate its approach to AT1 receptor. Its high docking score to AT1 receptor stems from more hydrophobic interactions compared to losartan. X-ray powder diffraction (XRPD) and thermogravimetric analysis (TGA) have shown that BV6 has a crystalline form that is not decomposed completely up to 600°C. These properties are desirable for a drug molecule. BV6 can also be incorporated into a mesoporous silicate drug-delivery matrix SBA-15. The properties of the obtained drug-delivery system have been inspected by XRD, (13)C CP/MAS, TGA and nitrogen sorption experiments.
authors.affiliation: Eldrug S.A., Patras Science Park, Stadiou, Platani, Rio Patras, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Agelis
authors.forename: A
authors.initials: A
authors.lastname: Resvani
authors.forename: D
authors.initials: D
authors.lastname: Ntountaniotis
authors.forename: P
authors.initials: P
authors.lastname: Chatzigeorgiou
authors.forename: C
authors.initials: C
authors.lastname: Koukoulitsa
authors.forename: M E
authors.initials: ME
authors.lastname: Androutsou
authors.forename: P
authors.initials: P
authors.lastname: Plotas
authors.forename: J
authors.initials: J
authors.lastname: Matsoukas
authors.forename: T
authors.initials: T
authors.lastname: Mavromoustakos
authors.forename: T
authors.initials: T
authors.lastname: Cendak
authors.forename: T Ukmar
authors.initials: TU
authors.lastname: Godec
authors.forename: G
authors.initials: G
authors.lastname: Mali
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D002462:Cell Membrane / Q000378:metabolism*; D016503:Drug Delivery Systems; D008051:Lipid Bilayers / Q000378:metabolism*; D019808:Losartan / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000494:pharmacology*; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry* / Q000378:metabolism; D012822:Silicon Dioxide / Q000378:metabolism*; D013059:Spectrum Analysis, Raman; D013818:Thermogravimetry; D014961:X-Ray Diffraction
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; C582180:BV6 peptide; D008051:Lipid Bilayers; D009842:Oligopeptides; D044140:Receptor, Angiotensin, Type 1; C509969:SBA-15; D012822:Silicon Dioxide; D019808:Losartan