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Macrolactonolides: a novel class of anti-inflammatory compounds
Linda Tomašković1, Marijana Komac, Oresta Makaruha Stegić
1GlaxoSmithKline Research Centre Limited, Prilaz baruna Filipovića 29, HR-10000 Zagreb, Croatia. Linda.Tomaskovic@glpg.com
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.
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