Macrolactonolides: a novel class of anti-inflammatory compounds

  • Bioorg Med Chem. 2013 Jan 1;21(1):321-32. doi: 10.1016/j.bmc.2012.10.036.
Linda Tomašković  1 ,  Marijana Komac ,  Oresta Makaruha Stegić ,  Vesna Munić ,  Jovica Ralić ,  Barbara Stanić ,  Mihailo Banjanac ,  Stribor Marković ,  Boška Hrvačić ,  Hana Čipčić Paljetak ,  Jasna Padovan ,  Ines Glojnarić ,  Vesna Eraković Haber ,  Milan Mesić ,  Mladen Merćep
Affiliations
  • 1. GlaxoSmithKline Research Centre Limited, Prilaz baruna Filipovića 29, HR-10000 Zagreb, Croatia. [email protected]
PMID: 23199485 DOI: 10.1016/j.bmc.2012.10.036
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.