title: Synthesis and biological evaluation of boswellic acid-NSAID hybrid molecules as anti-inflammatory and anti-arthritic agents.
abstract: Methyl esters of the β-boswellic acid (BA) and 11-keto-β-boswellic acid (KBA) obtained from Boswellia serrata resin were subjected to Steglich esterification with the different non-steroidal anti-inflammatory drugs (NSAID) viz., ibuprofen, naproxen, diclophenac and indomethacin. The novel hybrids of methyl boswellate (5-8) and that of methyl 11-keto boswellate (9-12) were evaluated for anti-inflammatory activity by carrageenan-induced rat hind paw edema model and anti-arthritic activity by Complete Freund's Adjuvant (CFA) induced arthritis in Wister albino rat. Significant inhibition on carrageenan-induced paw edema has been observed with 5, 6 and 10 where as in CFA induced rats, hybrids 5, 8, 9 and 12 exhibited pronounced antiarthritic activity. Hybrid molecules 5 and 9 have been found to be more effective in inhibiting in-vivo COX-2 than ibuprofen by itself, thus showing the synergistic effect. Hybrid 5 and 9 tested for in-vitro lipoxygenase and cyclooxygenase-2 (LOX/COX-2) inhibitory activity. The studies revealed that both 5 and 9 inhibited COX-2 relatively better than LOX enzyme.
authors.affiliation: Chemical Sciences Division, Vittal Mallya Scientific Research Foundation, BTM II Stage, Bangalore 560076, India.
authors.forename: Suvarna
authors.initials: S
authors.lastname: Shenvi
authors.affiliation: Department of Biological Sciences, Vittal Mallya Scientific Research Foundation, BTM II Stage, Bangalore 560076, India.
authors.forename: K R
authors.initials: KR
authors.lastname: Kiran
authors.affiliation: Department of Biological Sciences, Vittal Mallya Scientific Research Foundation, BTM II Stage, Bangalore 560076, India.
authors.forename: Krishna
authors.initials: K
authors.lastname: Kumar
authors.affiliation: Department of Biological Sciences, Vittal Mallya Scientific Research Foundation, BTM II Stage, Bangalore 560076, India.
authors.forename: Latha
authors.initials: L
authors.lastname: Diwakar
authors.affiliation: Chemical Sciences Division, Vittal Mallya Scientific Research Foundation, BTM II Stage, Bangalore 560076, India. Electronic address: gcreddy@vmsrf.org.
authors.forename: G Chandrasekara
authors.initials: GC
authors.lastname: Reddy
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D001168:Arthritis / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014315:Triterpenes; C054625:boswellic acid
keywords: Anti-arthritic; Anti-inflammatory; Boswellia serrata; Boswellic acids; NSAIDs