title: New synthesis of 6[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid and evaluation of the influence of adamantyl group on the DNA binding of a naphthoic retinoid.
abstract: 6[3-(1-Adamantyl)-4-methoxyphenyl]-2-naphthoic acid (Adapalene®), a synthetic aromatic retinoid specific for RARβ and RARγ receptors, has been prepared utilizing a Pd/C-mediated Suzuki coupling between 6-bromo-2-naphthoic acid and 4-methoxyphenyl boronic acid, followed by introduction of an adamantyl group in the position 3 of the formed 6-(4-methoxyphenyl)-2-naphthoic acid. The interaction of 6-(4-methoxyphenyl)-2-naphthoic acid/ethyl ester and the 3-adamantyl analogs with DNA was studied in aqueous solution at physiological conditions by UV-vis spectroscopy. The calculated binding constants K(ligand-DNA) ranged between 1.1×10(4) M(-1) and 1.1×10(5) M(-1), the higher values corresponding to those of the adamantylated compounds. Molecular modeling studies have emphasized that the intercalative binding of adapalene and its derivatives to DNA is mainly stabilized by hydrophobic interactions related to the presence of the adamantyl group.
authors.affiliation: Foundation for Research in Life Sciences c/o Insubrias Park, Via Roberto Lepetit 34, 21040 Gerenzano, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Milanese
authors.forename: Elena
authors.initials: E
authors.lastname: Gorincioi
authors.forename: Mehdi
authors.initials: M
authors.lastname: Rajabi
authors.forename: Giulio
authors.initials: G
authors.lastname: Vistoli
authors.forename: Enzo
authors.initials: E
authors.lastname: Santaniello
mesh_terms: D000218:Adamantane / Q000737:chemistry*; D000068816:Adapalene; D002384:Catalysis; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D007854:Lead / Q000737:chemistry; D008958:Models, Molecular; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D012176:Retinoids / Q000737:chemistry* / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D000097768:Retinoic Acid Receptor gamma
chemical_list: D000218:Adamantane; D000068816:Adapalene; D004247:DNA; D007854:Lead; D009281:Naphthalenes; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D000097768:Retinoic Acid Receptor gamma; C082925:retinoic acid receptor beta