ABSTRACT
One of the important aims of drug discovery for cancer is to find therapeutic agents from natural products that are effective and safe for cancer treatment. In the current study, an alkaloid, 2-acetyl-benzylamine, isolated from Adhatoda vasica, was screened for potent anticancer properties against leukemia cells. We used seven different types of leukemia cells such as CEM, NB-4, MOLM-14, Jurkat, IM-9, K562 and HL-60 for cytotoxic studies. 2-acetyl-benzylamine showed significant cytotoxic properties against MOLM-14 and NB-4 cells with IC50 values of 0.40 and 0.39mM at 24h when compared to other tested cells, respectively. Apoptosis was confirmed by annexin V-FITC/PI kit using flow cytometry and confocal microscope in MOLM-14 and NB-4 cells. In addition, 2-acetyl-benzylamine induced cell cycle arrest at G2/M phase in MOLM-14 cells and G0/G1 phase in NB-4 cells. Apoptosis mechanism was confirmed by RT-PCR and Western blot analysis. Treatment with 2-acetyl-benzylamine decreased the Bcl-2 activity and increased the Bax expression; cytochrome c was released and caspases-3 was activated in MOLM-14 and NB-4 cells. Besides, 2-acetyl-benzylamine inhibited the expression of JAK2/STAT3 in MOLM-14 and NB-4 cells. In vivo administration of 2-acetyl-benzylamine inhibited the growth of MOLM-14 cells in xenograft mice model. Molecular docking study has been performed to investigate the binding mode and to estimate the binding energy of 2-acetyl-benzylamine with the active site of JAK-2, AKT1, FLT3 and Bcl-2. The above findings proved that 2-acetyl-benzylamine could be developed as a potential therapeutic agent against cancer.
Subject(s)
Acetophenones/pharmacology , Antineoplastic Agents/pharmacology , Benzylamines/pharmacology , Justicia/chemistry , Plant Extracts/pharmacology , Plant Leaves/chemistry , Animals , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Female , HL-60 Cells , Humans , Janus Kinase 2/metabolism , Jurkat Cells , K562 Cells , Mice , Mice, Inbred BALB C , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , STAT3 Transcription Factor/metabolism , fms-Like Tyrosine Kinase 3/metabolismABSTRACT
A new gallic acid derivative, 1-O-galloyl-6-O-(4-hydroxy-3,5-dimethoxy)benzoyl-beta-D-glucose (1) has been isolated from an H2O-fraction of MeOH extract of Combretum quadrangulare seeds. Compound 1 exhibited potent hepatoprotective activity against D-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes with an IC50 of 3.3 microM.
Subject(s)
Glycosides/isolation & purification , Liver Diseases/prevention & control , Liver/drug effects , Plant Extracts/chemistry , Plants, Medicinal/chemistry , Animals , Apoptosis/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Galactosamine/metabolism , Glycosides/chemistry , Glycosides/pharmacology , Glycosides/therapeutic use , Hepatocytes/drug effects , Liver/cytology , Mice , Molecular Structure , Seeds/chemistry , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Five novel highly oxygenated diterpenes, orthosiphols K (1), L (2), M (3), and N (4) and norstaminone A (5), were isolated from the aerial part of Orthosiphon stamineus, together with three known diterpenes, orthosiphols A (6) and B (7) and neoorthosiphol A (8). Orthosiphol L (2) is an isopimarane-type diterpene with a hydroxyl group at C-12, which supports the biogenesis of staminane-type diterpenes, i.e., migration of a vinylic group from C-13 of isopimarane to C-12. Norstaminone A (5) has a staminane carbon framework and supports the biosynthetic pathway from staminols to norstaminols via staminolactones. All the isolated compounds showed mild to weak antiproliferative activities toward highly liver metastatic colon 26-L5 carcinoma and human HT-1080 fibrosarcoma cell lines.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Diterpenes/isolation & purification , Lamiaceae/chemistry , Plants, Medicinal/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cell Division/drug effects , Diterpenes/chemistry , Diterpenes/pharmacology , Drug Screening Assays, Antitumor , Humans , Magnetic Resonance Spectroscopy , Myanmar , Phenols/chemistry , Phenols/isolation & purification , Spectrometry, Mass, Fast Atom Bombardment , Spectrophotometry, InfraredABSTRACT
Chromatographic separation of part of an EtOH extract of the seeds of Alpinia blepharocalyx resulted in the isolation of six new (1-6) and two known (7, 8) diarylheptanoids together with 12 known compounds. The structures of the new compounds, including their absolute stereochemistry, were elucidated by spectroscopic and chemical methods as (3S,5S)- (1) and (3S,5R)-3-hydroxy-5-methoxy-1-(4-hydroxyphenyl)-7-phenyl-6E-heptene (2), (3S,5S)- (3) and (3S,5R)-3-hydroxy-5-ethoxy-1-(4-hydroxyphenyl)-7-phenyl-6E-heptene (4), (3S)-methoxy-1,7-bis(4-hydroxyphenyl)-6E-hepten-5-one (5), and 1,7-bis(4-hydroxyphenyl)hepta-4E,6E-dien-3-one (6). Among the isolated compounds, 5, (3S,5S)-3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)heptane (8), 4'-hydroxy-5,6-dehydrokawain (14), and/or phloroglucinol (20) showed significant antiproliferative activity against murine colon 26-L5 carcinoma (ED(50): 5, 5.2 microM; 8, 12.8 microM; 14, 20.7 microM; 20, 26.4 microM) and human HT-1080 fibrosarcoma (ED(50): 5, 10.1 microM; 14, 20.1 microM; 20, 20.9 microM) cells.
Subject(s)
Phenols/isolation & purification , Zingiberales/chemistry , Cell Division/drug effects , China , Drugs, Chinese Herbal/chemistry , Humans , Magnetic Resonance Spectroscopy , Molecular Structure , Phenols/chemistry , Plant Extracts/chemistry , Plants, Medicinal/chemistry , Seeds/chemistry , Tumor Cells, CulturedABSTRACT
From the MeOH extract of the aerial part of Vietnamese Orthosiphon stamineus, five new isopimarane-type diterpenes [orthosiphols F-J (1-5)] and two new diterpenes [staminols A (6) and B (7)] with a novel carbon-framework, to which we proposed the name "staminane", and three new highly-oxygenated staminane-type diterpenes [staminolactones A (8) and B (9) and norstaminol A (10)1 were isolated. Moreover, staminolactone A (8) is 8,14-secostaminane-type and staminolactone B (9) is 13,14-secostaminane-type, while norstaminol A (10) is 14-norstaminen-type. Together with these new diterpenes, sixteen known compounds were also isolated and identified to be: 7,3',4'-tri-O-methylluteolin (11), eupatorin (12), sinensetin (13), 5-hydroxy-6,7,3',4'-tetramethoxyflavone (14), salvigenin (15), ladanein (16), tetramethylscutellarein (17), 6-hydroxy-5,7,4'-trimethoxyflavone (18), vomifoliol (19), aurantiamide acetate (20), rosmarinic acid (21), caffeic acid (22), oleanolic acid (23), ursolic acid (24), betulinic acid (25), and beta-sitosterol (26). All the isolated compounds were tested for their cytotoxicity towards highly liver metastatic murine colon 26-L5 carcinoma cells, and the new diterpenes, except for 4, and flavonoids (11, 12, 16, 18) showed cytotoxicity with an ED50 value between 10 and 90 microg/ml.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Diterpenes/isolation & purification , Plants, Medicinal/chemistry , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes/chemistry , Diterpenes/pharmacology , Drug Screening Assays, Antitumor , Magnetic Resonance Spectroscopy , Mice , Molecular Structure , Plant Extracts/analysis , Tumor Cells, Cultured , VietnamABSTRACT
Six new triterpene glucosides, quadranosides VI-XI (1-6), belonging to three different [ursane- (1-4), oleanane- (5) and lupane-type (6)] triterpene classes, have been isolated from a MeOH extract of the seeds of Combretum quadrangulare KURZ (Combretaceae), together with nine known compounds, rosamutin (7), 28-O-beta-D-glucopyranosyl-6beta,23-dihydroxytormentic acid (8), arjunetin (9), arjunglucoside II (10), combreglucoside (11), chebuloside II (12), vitexin (13), (+)-catechin (14) and (-)-epigallocatechin (15). The structures of these compounds were elucidated by spectroscopic analysis.