title: Macrolactonolides: a novel class of anti-inflammatory compounds.
abstract: A new concept in design of safe glucocorticoid therapy was introduced by conjugating potent glucocorticoid steroids with macrolides (macrolactonolides). These compounds were synthesized from various steroid 17β-carboxylic acids and 9a-N-(3-aminoalkyl) derivatives of 9-deokso-9a-aza-9a-homoeritromicin A and 3-descladinosyl-9-deokso-9a-aza-9a-homoeritromicin A using stable alkyl chain. Combining property of macrolides to preferentially accumulate in immune cells, especially in phagocyte cells, with anti-inflammatory activity of classic steroids, we designed molecules which showed good anti-inflammatory activity in ovalbumin (OVA) induced asthma in rats. The synthesis, in vitro and in vivo anti-inflammatory activity of this novel class of compounds are described.
authors.affiliation: GlaxoSmithKline Research Centre Limited, Prilaz baruna Filipovića 29, HR-10000 Zagreb, Croatia. Linda.Tomaskovic@glpg.com
authors.forename: Linda
authors.initials: L
authors.lastname: Tomašković
authors.forename: Marijana
authors.initials: M
authors.lastname: Komac
authors.forename: Oresta
authors.initials: O
authors.lastname: Makaruha Stegić
authors.forename: Vesna
authors.initials: V
authors.lastname: Munić
authors.forename: Jovica
authors.initials: J
authors.lastname: Ralić
authors.forename: Barbara
authors.initials: B
authors.lastname: Stanić
authors.forename: Mihailo
authors.initials: M
authors.lastname: Banjanac
authors.forename: Stribor
authors.initials: S
authors.lastname: Marković
authors.forename: Boška
authors.initials: B
authors.lastname: Hrvačić
authors.forename: Hana
authors.initials: H
authors.lastname: Čipčić Paljetak
authors.forename: Jasna
authors.initials: J
authors.lastname: Padovan
authors.forename: Ines
authors.initials: I
authors.lastname: Glojnarić
authors.forename: Vesna
authors.initials: V
authors.lastname: Eraković Haber
authors.forename: Milan
authors.initials: M
authors.lastname: Mesić
authors.forename: Mladen
authors.initials: M
authors.lastname: Merćep
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy*; D002264:Carboxylic Acids; D002460:Cell Line; D015195:Drug Design; D005938:Glucocorticoids / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D018942:Macrolides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D011914:Rats, Inbred BN; D013256:Steroids / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D002264:Carboxylic Acids; D005938:Glucocorticoids; D018942:Macrolides; D013256:Steroids