Synthesis of new analogs of AKBA and evaluation of their anti-inflammatory activities

Publication date: 15 February 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 4
Author(s): Bharani Meka, Suryachandra Rao Ravada, Muthyala Murali Krishna Kumar, Kurre Purna Nagasree, Trimurtulu Golakoti
A new series of 11-keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic acid analogs (5, 7, 8, 10, 13, 18a-d, 27a-c, 28a-d) were synthesized by modification of hydroxyl and acid functional moieties of boswellic acids. The structures of these analogs were confirmed by spectral data analysis (¹H, ¹³C NMR and mass). Compounds 18b, 27a and 8 showed potent 5-lipoxygenase enzyme inhibitory activity (IC50: 19.53, 20.31 and 44.14μg/mL). The computational studies revealed that selectivity of AKBA is due to its fitment into the 5-LOX receptor, which is missing for the other enzymes like 12-LOX, COX-1 and COX-2. Our study found potentiating effects of 2-formyl and 3-keto substituents in reviving inactive AKBA analogues possessing essential COOH group at 4th position.

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