ABSTRACT
Icaritin is an active ingredient in Epimedium, which has a variety of pharmacological activities. However, the low activity of Icaritin and the unclear target greatly limit its application. Therefore, based on the structure of Icaritin, we adopted the strategy of replacing toxic groups and introducing active groups to design and synthesize a series of new analogues. The top compound C3 exhibited better antimultiple myeloma activity with an IC50 of 1.09 µM for RPMI 8226 cells, induced RPMI 8226 apoptosis, and blocked the cell cycle in the S phase. Importantly, transcriptome analysis, cellular thermal shift assay, and microscale thermophoresis assay confirmed that DEPTOR was the target of C3. Moreover, we explored its binding mode with C3. Especially, C3 displayed satisfactory inhibition of tumor growth in RPMI 8226 xenografts without obvious side effects. In summary, C3 was discovered as a novel putative inhibitor of DEPTOR for the treatment of multiple myeloma.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Design , Flavonoids/pharmacology , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Multiple Myeloma/drug therapy , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Epimedium/chemistry , Flavonoids/chemical synthesis , Flavonoids/chemistry , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Molecular Structure , Multiple Myeloma/metabolism , Structure-Activity RelationshipABSTRACT
The root of Cynanchum auriculatum (C. auriculatum) Royle ex Wight has been shown to possess various pharmacological effects and has recently attracted much attention with respect to its potential role in antitumor activity. The C-21 steroidal glycosides are commonly accepted as the major active ingredients of C. auriculatum. In this study, the antitumor abilities of different extracted fractions of the root bark and the root tuber of C. auriculatum were investigated by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in human cancer cell lines HepG2 and SMMC-7721. The results showed that the chloroform and ethyl acetate fractions of the root tuber suppressed tumor cell growth strongly. To identify and characterize the chemical constituents of different active fractions, an ultra high performance liquid chromatography with triple-quadrupole tandem mass spectrometry method was developed for the simultaneous quantitation of eight C-21 steroidal glycosides. The analysis revealed that the C-21 steroidal glycosides were concentrated in the chloroform and ethyl acetate fractions, and the total contents of different fractions in the root tuber were significantly higher than those of corresponding ones in the root bark. Furthermore, the C-21 steroidal glycosides based on different types of aglucones were prone in different medicinal parts of C. auriculatum.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Cynanchum/chemistry , Glycosides/isolation & purification , Plant Roots/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Drug Screening Assays, Antitumor , Glycosides/pharmacology , Humans , Plant Extracts/chemistry , Tandem Mass SpectrometryABSTRACT
Two new compounds, 5ß-pregnane-2α,6α,20(S)-triol (1) and 8-hydroxyl-3-methoxyl-2(1H)-quinolone (2), were isolated from Scolopendra multidens Newport. Their structures were elucidated on the basis of spectroscopic methods including 1D and 2D NMR and HR-TOF-MS.
Subject(s)
Arthropods/chemistry , Pregnanetriol/analogs & derivatives , Quinolones/isolation & purification , Animals , China , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Pregnanetriol/chemistry , Pregnanetriol/isolation & purification , Quinolones/chemistryABSTRACT
OBJECTIVE: To study the chemical constituents in the fruits of Acanthopanax gracilistylus. METHODS: The chemical components were isolated and purified by silica gel, ODS C-18, and Sephadex LH-20 column chromatogram. The chemical structures were elucidated on the basis of physicochemical properties and spectral data. RESULTS: Ten compounds were isolated and identified as acankoreoside D(1), 3alpha, 11alpha-dihydroxylup-20(29)-en-28-oic acid(2), 3/3-([O-beta-D-glucopyranuronosyl] oxy) -olean-12-ene-28-olc acid (3),3beta-([O-beta-D-glucopyranuronosyl]oxy)-28-O-P3-D-glucopyranosyl-olean-12-ene-28-olc acid(4),oleanolic acid-3-O-6'-O-methyl-beta-D-glucuronopyranoside(5), acantrifoside A(6), acankoreoside A(7), (-)-kaur-16-en-19-oic acid(8), protocatechuic acid (9),beta-sitosterol(10). CONCLUSION: Compounds 2-5 are obtained from the fruits of the plant for the first time.
Subject(s)
Eleutherococcus/chemistry , Fruit/chemistry , Plants, Medicinal/chemistry , Saponins/isolation & purification , Triterpenes/isolation & purification , Ethanol/chemistry , Hydroxybenzoates/chemistry , Hydroxybenzoates/isolation & purification , Magnetic Resonance Spectroscopy , Saponins/chemistry , Sitosterols/chemistry , Sitosterols/isolation & purification , Triterpenes/chemistryABSTRACT
The chemical constituents of Chinese red ginseng (Panax ginseng) were investigated. The chemical constituents were isolated and purified by silca gel, ODS, and Sephedex LH-20, column chromatography, and preparative HPLC. Their chemical structures were elucidated on the basis of physicochemical properties and spectra data. Fourteen compounds were isolated and identified as: notoginsenoside R2 (1), 20(S) -ginsenoside Rg3 (2), 20(R) -ginsenoside Rg3 (3), 20 (S)-ginsenoside Rg2 (4), 20(R) -ginsenosideRg2 (5), 20 (S)-ginsenoside Rh1 (6), 20(R) -ginsenoside Rh1 (7), ginsenoside Rh4 (8), -Ro (9), -Rb1 (10), -Rg1 (11), Re-(12), Rf (13), maltol (14). Compounds 1, 4, 6, were obtained from red ginseng for the first time. Compounds 2 and 3, 4 and 5-7 were enantiomers respectively, enantiomers 6 and 7 were isolated as monomer for the first time.
Subject(s)
Ginsenosides/analysis , Panax/chemistry , Ginsenosides/chemistry , StereoisomerismABSTRACT
OBJECTIVE: To investigate the chemical constituents in Cicuta virosa var. latisecta. METHOD: Many kinds of column chromatography were used to isolate the compounds from the EtOH ext. of C. virosa var. latisecta. The chemical constituents of the plant were identified by means of IR, MS, 1H-NMR, 13C-NMR, respectively, in some case by direct comparison with authentic samples. RESULT: Nine compounds were isolated from the aerial part and were identified as: 3beta-acetyloxy-16-hydroxy-olean-12-en-28-oic acid (1), 9 (11), 12-dieneoleana-3beta-ol (2), 9, 19-cyclolanaost-24-en-3-one (3), 9, 19-cycloergost-23-en-3, 25-diol (4), stigmasterol (5), falcarindiol (6), 1, 2-benzenedicarboxylic acid, his (2-ethylhexyl) ester (7), stigmast-5-en-3beta-ol (8), beta-daucosterol (9). CONCLUSION: Compound 1 is a new natural product, and compounds 2 to 9 were firstly isolated from this plant.
Subject(s)
Cicuta/chemistry , Organic Chemicals/analysis , Organic Chemicals/isolation & purification , Plant Components, Aerial/chemistryABSTRACT
AIM: To detect the hepatotoxic pyrrolizidine alkaloids (HPA) in the genus Ligularia Cass.. METHODS: The alkaloid extracts of Ligularia plant materials were detected and analyzed by the method of combination of TLC, and LC/MSn. RESULTS: Among 22 species of Ligularia Cass., HPA were detected in 18 species with LC/MSn, and no HPA was detected in the remaining 4 species. CONCLUSION: HPA was first detected with LC/MSn in L. tongelensis and other 15 species of Ligularia Cass.; HPA from these plants should be isolated, separated and identified and it is necessary to study the activities and toxicities of the HPA. The types and kinds of HPA from different species and sources are different, they should be detected separately.
