Structural basis for developing multitarget compounds acting on Cysteinyl Leukotriene Receptor 1 and G-Protein coupled Bile Acid Receptor 1
Informazioni aggiuntive
Autori
Fiorillo B.,
Sepe V.,
Conflitti P.,
Roselli R.,
Biagioli M.,
Marchianò S.,
De Luca P.,
Baronissi G.,
Rapacciuolo P.,
Cassiano C.,
Catalanotti B.,
Zampella A.,
Limongelli V.,
Fiorucci S.
Tipo
Articolo pubblicato in rivista scientifica
Anno
2021
Lingua
Inglese
Sommario
G-protein-coupled receptors (GPCRs) are the molecular target of 40% of marketed drugs and the most investigated structures to develop novel therapeutics. Different members of the GPCRs superfamily can modulate the same cellular process acting on diverse pathways, thus representing an attractive opportunity to achieve multitarget drugs with synergic pharmacological effects. Here, we present a series of compounds with dual activity toward cysteinyl leukotriene receptor 1 (CysLT1R) and G-protein-coupled bile acid receptor 1 (GPBAR1). They are derivatives of REV5901─the first reported dual compound─with therapeutic potential in the treatment of colitis and other inflammatory processes. We report the binding mode of the most active compounds in the two GPCRs, revealing unprecedented structural basis for future drug design studies, including the presence of a polar group opportunely spaced from an aromatic ring in the ligand to interact with Arg792.60 of CysLT1R and achieve dual activity.
Parole chiave
Binding modes, Chemical calculations, Ligands, Quinolines, Receptors
Periodico
Journal of Medicinal Chemistry
Volume
64
Numero ( Mese )
22
Pagine (o numero dell’articolo)
16512-16529
Diffusione
Licenza
Diritti riservati
Visibilità
Pubblico
Status open access
Green
