ABSTRACT
A new series of diaryl heptanones (12a-q) were synthesized and their structures were confirmed by its 1H, 13C NMR and Mass spectral data. These analogs were evaluated for their anti-oxidant activity and potential to inhibit 5-lipoxygenase. Compounds 12k and 12o showed potent in vitro 5-lipoxygenase enzyme inhibitory activity with IC50 values of 22.2, 21.5⯵M, which are comparable to curcumin (24.4⯵M). Further they also have shown significant antioxidant activity. Molecular docking studies clearly showed correlation between binding energy and potency of these compounds.
Subject(s)
Arachidonate 5-Lipoxygenase/metabolism , Diarylheptanoids/chemistry , Diarylheptanoids/pharmacology , Lipoxygenase Inhibitors/chemistry , Lipoxygenase Inhibitors/pharmacology , Antioxidants/chemical synthesis , Antioxidants/chemistry , Antioxidants/pharmacology , Arachidonate 5-Lipoxygenase/chemistry , Curcumin/pharmacology , Diarylheptanoids/chemical synthesis , Humans , Inhibitory Concentration 50 , Lipoxygenase Inhibitors/chemical synthesis , Molecular Docking SimulationABSTRACT
Isolation and characterisation of two new eudesmanolides, 5α-hydroperoxy-7α-hydroxy-isosphaerantholide (1) and (11α,13-dihydro-7α-hydroxyfrullanolide-13-yl)-adenine (2) from the flower heads of Sphaeranthus indicus are described. In addition, 5α-hydroxy-isosphaerantholide (3) and 11α,13-dihydro-eudesman-3,5,7-triene-6α-12-olide (4) are reported first time as a metabolite of S. indicus and as a natural product, respectively. The structures of these compounds were established from rigorous analysis of their high-resolution mass, IR, UV, 1H NMR, 13C NMR and 2D NMR spectral data.
Subject(s)
Adenine/analogs & derivatives , Asteraceae/chemistry , Sesquiterpenes/chemistry , Sesterterpenes/chemistry , Adenine/chemistry , Magnetic Resonance Spectroscopy , Sesquiterpenes/isolation & purification , Spectrophotometry, UltravioletABSTRACT
A new series of 11-keto-ß-boswellic acid and 3-O-acetyl-11-keto-ß-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.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Arachidonate 5-Lipoxygenase/metabolism , Lipoxygenase Inhibitors/pharmacology , Triterpenes/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Dose-Response Relationship, Drug , Humans , Lipoxygenase Inhibitors/chemical synthesis , Lipoxygenase Inhibitors/chemistry , Molecular Structure , Structure-Activity Relationship , Triterpenes/chemical synthesis , Triterpenes/chemistryABSTRACT
Chromolaena odorata (Syn: Eupatorium odoratum) is a perennial plant belonging to the Asteraceae family. Extracts of C. odorata have shown strong anti-oxidant and moderate anti-adipogenenesis activities. Detailed phytochemical investigation of C. odorata led to the isolation of 21 secondary metabolites, which include a new flavanone (3), and a chalcone, 3,2'-dihydroxy-4,4',5',6'-tetramethoxychalcone (2), reported for the first time from a natural source, besides three known compounds 1, 4 and 5, all of which are reported for the first time from C. odorata. Some of these compounds exhibited potent anti-oxidant and anti-adipogenesis activities and these may be partly responsible for the activity of the extract.
