ABSTRACT
Chemical investigation of the stems of Dulacia egleri resulted in the isolation of eglerisine (1: ), a compound with a rare sesquiterpenoid tropolone skeleton. Its structure was determined by analysis of spectrometric and spectroscopic data, including HRESIMS, 1D, and 2D NMR. The antiproliferative effects of eglerisine were tested in human leukemia lineages. In the Kasumi-1 lineage, an acute myeloid leukemia cell line, eglerisine reduced cell metabolism, as determined by the resazurin assay. Eglerisine did not induce cell death by either apoptotic or necrotic mechanisms. However, a reduction of the absolute number of cells was observed. Eglerisine induced cell cycle arrest after 72 h of treatment by phosphorylation of H2AX histone, reducing the S phase and increasing the G2 phase of the cell cycle.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Cell Proliferation/drug effects , Olacaceae/chemistry , Plant Extracts/pharmacology , Sesquiterpenes/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cell Cycle/drug effects , Cell Line, Tumor , Histones/metabolism , Humans , Leukemia, Myeloid, Acute , Magnetic Resonance Spectroscopy , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacologyABSTRACT
A new flavone, 4'-hydroxy-6,7-methylenedioxy-3-methoxyflavone 1, and two other nucleosides, ribavirin 2 and adenosine 3, were isolated from the leaves of Dulacia egleri. The nucleosides were identified by spectroscopic techniques (1D, 2D-NMR) while the structure of the flavonoid was established by 1D, 2D-NMR analysis, including HRESIMS data. The results obtained in the biological assays showed that the compound 1 was able to inhibit cathepsins B and L with IC50 of 14.88⯱â¯0.18⯵M and 3.19⯱â¯0.07⯵M, respectively. The mechanism of inhibition for both enzymes were determined showing to be competitive at cathepsin B with Kiâ¯=â¯12.8⯱â¯0.6⯵M and non-linear non-competitive with positive cooperativity inhibition at cathepsin L with Kiâ¯=â¯322⯱â¯33⯵M, αKiâ¯=â¯133⯱â¯15⯵M, ßKiâ¯=â¯5.14⯱â¯0.41⯵M and γKiâ¯=â¯13.2⯱â¯13⯵M.
Subject(s)
Cathepsin B/antagonists & inhibitors , Cathepsin L/antagonists & inhibitors , Enzyme Inhibitors/chemistry , Flavonoids/chemistry , Olacaceae/chemistry , Brazil , Enzyme Inhibitors/isolation & purification , Enzyme Inhibitors/pharmacology , Flavonoids/isolation & purification , Flavonoids/pharmacology , Molecular Structure , Plant Leaves/chemistryABSTRACT
The study about Eugenia dysenterica led to the isolation of 3-acetyl-urs-12-en-28-oic (1), 3-acetyl-olean-12-en-28-oic acid (2) and isoquercetin (3) from the stem barks, and of 3-O-ß-glucopyranosyl-ß-sitosterol (4), methyl 3-hydroxy-4-methoxybenzoate (5), methyl 4-hydroxyphenyl propionate (6), E-methyl-4-hydroxycinnamate (7), quercetin-3-O-(6êê-O-galloyl)-ß-d-glucopyranoside (8) and quercetin-3-O-ß-d-galactopyranoside (9) from the leaves. The structures 1-9 were set through the analysis of their NMR spectroscopic data. Compounds 2, 3 and 5-8 were reported for the first time in the Eugenia genus. Compound 8 reduced cell viability and presented IC50 values 40.3 and 36.7 µM, for the CCRF-CEM and the Kasumi-1 cells, respectively.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Eugenia/chemistry , Leukemia/drug therapy , Cell Line, Tumor , Drug Screening Assays, Antitumor , Flavonoids/chemistry , Flavonoids/pharmacology , Galactosides/chemistry , Galactosides/pharmacology , Humans , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Oleanolic Acid/chemistry , Plant Bark/chemistry , Plant Extracts/chemistry , Plant Leaves/chemistry , Quercetin/analogs & derivatives , Quercetin/chemistry , Quercetin/pharmacologyABSTRACT
A new orbitide named [1-8-NαC]-zanriorb A1 (1) was isolated and characterized from the leaves of Zanthoxylum riedelianum using NMR and mass spectrometry. The absolute configuration of the amino acids was determined using Marfey's method on the acid hydrolysates. Compound 1 induced cell death by apoptosis in Jurkat leukemia T cells (IC50 218 nM).
