Macrolactonolides: a novel class of anti-inflammatory compounds.
Tomašković L, Komac M, Makaruha Stegić O, Munić V, Ralić J, Stanić B, Banjanac M, Marković S, Hrvačić B, Čipčić Paljetak H, Padovan J, Glojnarić I, Eraković Haber V, Mesić M, Merćep M.
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.