Isolation and Structure-Activity Relationship Study of Anti-Inflammatory Terpenoids from Boswellia dalzielii Stem Bark, North West Nigeria

Boswellia dalzielii is a pharmacologically significant tree distributed across the dry savannah zones of North West Nigeria, particularly in Sokoto and Zamfara States, where its bark resins are used by traditional healers for rheumatoid arthritis, inflammatory joint disease, and asthma. Boswellic acids from the related Boswellia serrata have been well characterised for 5-lipoxygenase inhibitory activity, but Nigerian B. dalzielii remains phytochemically underexplored and no structure-activity relationship (SAR) data exist for its terpenoid constituents. This PhD research isolates the anti-inflammatory terpenoids of Boswellia dalzielii stem bark and systematically defines their structure-activity relationships against leukotriene biosynthesis and COX-2 pathways. Crude bark resin extract was fractionated by normal and reverse-phase column chromatography. Isolated terpenoids were characterised by 1H NMR, 13C NMR, HMBC, COSY, NOESY, and HRMS. A panel of 16 isolated and semi-synthetic terpenoid derivatives was evaluated for 5-LOX inhibitory activity, COX-2 selectivity, and NF-kB p65 nuclear translocation inhibition. Quantitative structure-activity analysis was performed using MOE software. Twelve pentacyclic triterpenoids were characterised, including three novel ursane-type acids. The 11-oxo-beta-boswellic acid analogue demonstrated the highest 5-LOX inhibition (IC50 0.43 uM). SAR analysis identified the 11-oxo function and A-ring hydroxylation as critical determinants of 5-LOX potency. Lead compounds were evaluated for CYP3A4 inhibition and ADMET parameters. This research establishes a pharmacophore model for 5-LOX inhibitory terpenoids from Nigerian Boswellia and identifies two semi-synthetic leads for anti-inflammatory drug development. Keywords: Boswellia dalzielii, terpenoids, structure-activity relationship, 5-lipoxygenase, North West Nigeria