title: Synthesis of new analogs of AKBA and evaluation of their anti-inflammatory activities.
abstract: 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.
authors.affiliation: Laila Impex R&D Center, Unit-I, Phase-III, Jawahar Auto Nagar, Vijayawada 520 007, Andhra Pradesh, India.
authors.forename: Bharani
authors.initials: B
authors.lastname: Meka
authors.affiliation: Laila Impex R&D Center, Unit-I, Phase-III, Jawahar Auto Nagar, Vijayawada 520 007, Andhra Pradesh, India.
authors.forename: Suryachandra Rao
authors.initials: SR
authors.lastname: Ravada
authors.affiliation: Department of Pharmaceutical Chemistry, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam 530 00, Andhra Pradesh, India.
authors.forename: Muthyala
authors.initials: M
authors.lastname: Murali Krishna Kumar
authors.affiliation: Department of Pharmaceutical Chemistry, AU College of Pharmaceutical Sciences, Andhra University, Visakhapatnam 530 00, Andhra Pradesh, India.
authors.forename: Kurre
authors.initials: K
authors.lastname: Purna Nagasree
authors.affiliation: Laila Impex R&D Center, Unit-I, Phase-III, Jawahar Auto Nagar, Vijayawada 520 007, Andhra Pradesh, India. Electronic address: research@lailanutra.in.
authors.forename: Trimurtulu
authors.initials: T
authors.lastname: Golakoti
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016859:Lipoxygenase Inhibitors; D014315:Triterpenes; C094432:acetyl-11-ketoboswellic acid; D001094:Arachidonate 5-Lipoxygenase; C583212:ALOX5 protein, human
keywords: 3-O-acetyl-11-keto-β-boswellic acid; 5-Lipoxygenase; Anti-inflammatory; Boswellia serrata