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
BACKGROUND: Sophora belongs to the family of Fabaceae and the species in this genus are currently used as a folklore medicine for preventing a variety of ailments including cancer. Our aim was to identify and validate an anticancer compound from Sophora interrupta using multi-spectroscopic, anticancer screening, and molecular docking approach. METHODS: The cytotoxicity of the various solvent extracts, petroleum ether, n-butanol, and ethyl acetate (EtOAc) of the S. interrupta root powder was evaluated in a breast cancer cell lines (MCF-7). The extract that had anticancer activity was subjected to column chromatography based on the polarity of the solvents. The anticancer activity of the elution fractions was validated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The isolated metabolite fraction with anticancer activity was run through a C18 column isocratic and gradient high-performance liquid chromatography (HPLC). The structure of the isolated compound was characterized using (1)H nuclear magnetic resonance (NMR), (13)C-NMR, Fourier transform infrared spectroscopy, and liquid chromatography-mass spectrometer methods. RESULTS: The crude EtAOc extract effectively inhibited the proliferation of MCF-7 cells. The column eluted chloroform and EtOAc (4:6) fraction of the EtOAc extract showed significant anticancer activity in the MCF-7 cells compared with normal mesenchymal stem cells. This fraction showed three major peaks in the HPLC chromatogram and the first major peak with a retention time (RT) of 7.153 was purified using preparative-HPLC. The structure of the compound is a piceatannol, which is a metabolic product of resveratrol. Piceatannol formed direct two hydrogen bond interactions between Cys912 (2H), and Glu878 of vascular endothelial growth factor receptor 1 (VEGFR1) with a glide-score (G-score) of -10.193, and two hydrogen bond interactions between Cys919, and Asp1046 of VEGFR2, with a G-score of -8.359. The structure is similar to that of the crystallized protein for VEGFR1 and R2. CONCLUSIONS: Piceatannol is a secondary metabolite of S. interrupta that has anticancer activity. Moreover, piceatannol has been isolated for the first time from S. interrupta.
