ABSTRACT
Four new lycoctonine-type C19-diterpenoid alkaloids kamaonensines H-K (1-4) have been isolated from the whole plants of Delphinium kamaonense, together with 12 known compounds (5-16). Interestingly, kamaonensines 1-3 contained a rare nitrone (immine N-oxide) moiety, respectively. Their structures were established by spectroscopic analyses. The active evaluation of compounds (1-16) by LPS induced RAW 264.7 macrophages showed that compounds 4 and 8 displayed strong anti-inflammatory activities. While compounds 11 and 12 also showed strong cytotoxicities by the RAW 264.7 cell viability assay.
ABSTRACT
A series of ß-carbolines possessing the aryl group at C-1 position has been synthesized from tryptophan. The newly synthesized compounds were screened for their in vitro anticancer activity against various human cancer cell lines by MTT assay. Some of them exhibited anticancer activity with IC50 values lower than 10µM outdistanced the cisplatin level. Structure-activity relationship reveals that the alcohol substituents at C-3 position played an important role in inhibition activity.
Subject(s)
Antineoplastic Agents/pharmacology , Carbolines/pharmacology , Neoplasms/pathology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Carbolines/chemical synthesis , Carbolines/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HL-60 Cells , Humans , Inhibitory Concentration 50 , MCF-7 Cells , Molecular Structure , Structure-Activity RelationshipABSTRACT
Tussilagone (TSL) and its allied sesquiterpenoids were considered as the main active principles of the flower buds of Tussilago farfara, which has been widely used in China as an antitussive herbal medicine. Six new bisabolane-type sesquiterpenoids, tussfararins A-F (1-6), along with 12 known sesquiterpenoids, were isolated from the flower buds of T. farfara. Structures of the new compounds were elucidated by extensive spectroscopic analysis. The biological analysis showed that compounds 1, 3, 6, and 7 inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells with IC50 values of 13.6-24.4 µM.
Subject(s)
Antitussive Agents/isolation & purification , Drugs, Chinese Herbal/isolation & purification , Lipopolysaccharides/adverse effects , Nitric Oxide/metabolism , Sesquiterpenes/isolation & purification , Tussilago/chemistry , Animals , Antitussive Agents/chemistry , Antitussive Agents/pharmacology , Cell Line, Tumor , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Flowers/chemistry , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Mice , Molecular Structure , Plants, Medicinal , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacologyABSTRACT
Five new vobasinyl-ibogan-type bisindole alkaloids, tabernaricatines A-E (1-5), two new monomers, tabernaricatines F and G (6 and 7), and 24 known indole alkaloids were isolated from the aerial parts of Tabernaemontana divaricata. Alkaloids 1 and 2 are the first vobasinyl-ibogan-type alkaloids possessing a six-membered ring via an ether linkage between C-17 and C-21. All compounds except for 3 were evaluated for their cytotoxicity against five human cancer cell lines; conophylline showed significant bioactivity against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cells with IC50 values of 0.17, 0.35, 0.21, 1.02, and 1.49 µM, respectively.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/pharmacology , Indole Alkaloids/isolation & purification , Indole Alkaloids/pharmacology , Tabernaemontana/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/chemistry , Female , HL-60 Cells , Humans , Indole Alkaloids/chemistry , Inhibitory Concentration 50 , Molecular StructureABSTRACT
Five new isopimarane diterpenoids, fokihodgins A-E (1-5), four new labdane diterpenoids, fokihodgins F-I (6-9), and one new icetexane diterpenoid, fokihodgin J (10), as well as 18 known diterpenoids were isolated from Fokienia hodginsii. The structures of the new compounds were determined on the basis of their spectroscopic analysis, and the absolute configurations of 1 and 6 were established by X-ray crystallographic analysis. Compound 9 showed moderate cytotoxicity against HL-60 and SMMC-7721 cell lines, with IC50 values of 9.10 and 7.50 µM, respectively.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Cupressaceae/chemistry , Diterpenes/isolation & purification , Drugs, Chinese Herbal/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Crystallography, X-Ray , Diterpenes/chemistry , Diterpenes/pharmacology , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , HL-60 Cells , Humans , Inhibitory Concentration 50 , Molecular Conformation , Molecular Structure , Plant Leaves/chemistry , Plant Stems/chemistryABSTRACT
Three new triterpenoids, kadcotriones A-C (1-3), together with the biogenetically related lanostane-type triterpenoid (4), were isolated from Kadsura coccinea. Compound 1 features a 12,14ß-dimethyl 6/6/6-fused tricyclic skeleton, while 2 and 3 are characterized by a 6/6/5-ring system. Their structures were determined by NMR and electronic circular dichroism spectroscopic methods. Compounds 2 and 4 exhibited anti-HIV-1 activities with EC50 values of 30.29 and 54.81 µM, respectively.
Subject(s)
Anti-HIV Agents/isolation & purification , Drugs, Chinese Herbal/isolation & purification , Kadsura/chemistry , Triterpenes/isolation & purification , Anti-HIV Agents/chemistry , Anti-HIV Agents/pharmacology , Circular Dichroism , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , HIV-1/drug effects , Molecular Structure , Plant Stems/chemistry , Triterpenes/chemistry , Triterpenes/pharmacologyABSTRACT
Five new compounds (1-5), including two limonoids, one triterpenoid, one steroid, and one sesquiterpenoid, along with nine known limonoids (6-14), were isolated from the bark of Melia azedarach. The structures of the new compounds were elucidated by 2D NMR spectroscopy and mass spectrometry. The isolated compounds as well as three acetylated derivatives of 9 were evaluated for their cytotoxicities against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480) by an MTT assay. Seven limonoids (1, 6, 7, 8, 9, 9b, and 9c) showed significant inhibitory activities against tested cell lines with IC50 values ranging from 0.003 to 0.555 µM, and their preliminary structure-activity relationships are also discussed.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Limonins/pharmacology , Melia azedarach/chemistry , Sesquiterpenes/pharmacology , Steroids/pharmacology , Triterpenes/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Inhibitory Concentration 50 , Limonins/chemistry , Limonins/isolation & purification , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Structure , Plant Bark/chemistry , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification , Steroids/chemistry , Steroids/isolation & purification , Structure-Activity Relationship , Triterpenes/chemistryABSTRACT
Two new ursane-type triterpenoids, 3ß,19α,23-trihydroxyurs-12-en-24-al-28-oic acid (1) and 3ß,19α,24-trihydroxy-23-norurs-12-en-28-oic acid (2), two new pregnane derivatives, 3ß,12ß-dihydroxy-5α-pregnane-14,16-dien-20-one (9) and 12ß-hydroxy-5α-pregnane-14,16-dien-3,20-dione (10), and eight known compounds were isolated from the twigs and leaves of Emmenopterys henryi. The structures of the new compounds were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR experiments. Compounds 4, 11, and 12 showed cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cell lines with IC50 values in the range of 3.11-20.12 µM.
Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Neoplasms/drug therapy , Phytotherapy , Plant Extracts/therapeutic use , Pregnanes/therapeutic use , Rubiaceae/chemistry , Triterpenes/therapeutic use , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , HL-60 Cells , Humans , MCF-7 Cells , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Leaves , Plant Stems , Pregnanes/chemistry , Pregnanes/isolation & purification , Pregnanes/pharmacology , Triterpenes/chemistry , Triterpenes/isolation & purification , Triterpenes/pharmacologyABSTRACT
Nine new alkaloids, melodinines M-U (1-9), and 11 known alkaloids were isolated from Melodinus suaveolens. The new structures were elucidated by extensive NMR and mass spectroscopic analyses and comparison to known compounds. All compounds were evaluated for their cytotoxicity against five human cancer cell lines. Compounds 6, 11, and 16 showed significant cytotoxicity.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Apocynaceae/chemistry , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/chemistry , Female , Humans , Indole Alkaloids/chemistry , Molecular Structure , Nuclear Magnetic Resonance, BiomolecularABSTRACT
The present paper describes the study of the phytochemical properties and anti-HIV activity of the phenolic isolates of the plateau medicinal plant Daphne acutiloba Rehd. (Thymelaeceae). Two new lignans named daphnenin (1) and daphnetone (2), along with 11 known ones, were isolated, and their structures were elucidated by 1D and 2DNMR spectroscopy aswell as HRESIMS. In the anti-HIV activity study, daphnenin (1) and caffeic acid n-octadecyl ester (13) showed definite anti-HIVactivity with EC(50) values of 0.39 and 0.16 µg/mL, respectively.
Subject(s)
Anti-Retroviral Agents/pharmacology , Caffeic Acids/pharmacology , Daphne/chemistry , HIV-1/drug effects , Lignans/isolation & purification , Lignans/pharmacology , Plant Extracts/pharmacology , Anti-Retroviral Agents/isolation & purification , Caffeic Acids/isolation & purification , Molecular Structure , Plant Extracts/chemistryABSTRACT
Three new phenolic compounds, eucalmaidin F (1), (3S)-5-guaiacyl-3-hydroxypentanoic acid (2), and 8-ß-C-glucopyranosyl-5,7-dihydroxy-2-isobutylchromone (3), were isolated from the branches of E. maideni, together with 30â known compounds, including four phenylpropanoids, three lignans, four phloroglucinol glucosides, five dihydroflavonoids, seven simple phenolic compounds, six terpenoids, and glycerol. The new structures were established by spectroscopic studies (MS, and 1D- and 2D-NMR), chemical degradation, and modified Mosher's method. Compounds 3, guaiacylglycerol, 3-hydroxy-1-(4-hydroxyphenyl)propan-1-one, caffeic acid, (2E)-3-(4-hydroxyphenyl)prop-2-enoic acid, (7'S,8R,8'R)-lyoniresinol, (+)-lyoresinol 3α-O-α-L-rhamnopyranoside, garcimangosone, phlorocetophenone 2'-glucopyranoside, (+)-taxifolin 3α-O-α-L-rhamnopyranoside, (+)-aromadendrin, (+)-taxifolin, resveratrol, piceatannol, 3,4,5-trihydroxyphenol. Tachiaside, gallic acid, macrocapals A und G, and oleuropeic acid were evaluated for their cytotoxicities against five human cancer cell lines. Resveratrol, piceatannol, gallic acid, and macrocapal G exhibited moderate inhibitory effects on human myeloid heukemia HL-60 cell, with IC(50) values of 22.05, 22.05, 7.75, and 31.93â µM, respectively; and only macrocapal G showed inhibitory effect on hepatocellular carcinoma SMMC-7721 cell, with an IC(50) value of 26.75â µM.
Subject(s)
Chromones/chemistry , Eucalyptus/chemistry , Flavones/chemistry , Phenols/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Chromones/isolation & purification , Chromones/pharmacology , Drug Screening Assays, Antitumor , Flavones/isolation & purification , Humans , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Conformation , Phenols/isolation & purification , Phenols/pharmacology , Plant Stems/chemistryABSTRACT
In the title compound, C(13)H(13)NO(4), the fused-ring system is nearly planar, with an r.m.s. deviation of 0.0408â Å. In the crystal, mol-ecules are linked into centrosymmetric dimers by a pair of N-Hâ¯O hydrogen bonds. The ethyl group is disordered over two positions in a ratio of 0.758â (6):0.242â (6).
ABSTRACT
Three series of novel ß-amino alcohols possessing an N-anthranyl group have been obtained using tryptophan as the major starting material. These compounds were screened for cytotoxic activity against five human cancer cell lines in vitro by MTT assay, and some of them exhibited potential ability to be anticancer agents. Structure-activity relationship was carefully investigated. Only the compounds possessing small substituents (H or CH(3)) at C-6 position showed the same activity as cisplatin (DDP) did.
Subject(s)
Amino Alcohols/chemistry , Antineoplastic Agents/chemical synthesis , Amino Alcohols/therapeutic use , Amino Alcohols/toxicity , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/toxicity , Cell Line, Tumor , Drug Design , Drug Screening Assays, Antitumor , Humans , Neoplasms/drug therapy , Structure-Activity RelationshipABSTRACT
Eight new neoclerodane diterpenoids (1- 8), scutebatas H-O, together with eight known compounds, have been isolated from the whole plant of Scutellaria barbata D. Don. Their structures were elucidated on the basis of spectroscopic studies. In vitro cytotoxicity of selected compounds against cancer cell lines HL-60, SMMC-7721, A-549, MCF-7, and SW480 was evaluated. Compounds 5, 6, 7 showed moderate cytotoxicities against several human cancer cell lines, with IC50 values ranging from 12.6-31.4 µM. In addition, compound 1 showed selective cytotoxicity against MCF-7.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes/pharmacology , Scutellaria/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Cell Survival , China , Diterpenes/chemistry , Diterpenes/isolation & purification , Diterpenes, Clerodane , Humans , Inhibitory Concentration 50 , Molecular Structure , Plant Components, Aerial/chemistryABSTRACT
New chalcone and dimeric chalcones with 1,4- P-benzoquinone residue, combrequinone A (1), combrequinone B (2), and combrequinone C (3), along with three known compounds (4-6), were isolated from the ethanolic extract of the stems and leaves of Combretum yunnanense, and their structures were determined by spectroscopic analysis. Compounds 1-3 were evaluated for in vitro cytotoxicity against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7, and SW480. Compounds 1, 2 and 3 were found to be most potent against HL-60 acute leukemia cells, with IC50 values of 4.63, 4.07, and 1.26 µM, respectively.
Subject(s)
Cell Survival/drug effects , Chalcones/pharmacology , Ferns/chemistry , Plant Extracts/pharmacology , Benzoquinones/chemistry , Cell Line, Tumor , Chalcones/chemistry , Humans , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Plant Extracts/chemistry , Plant Leaves/chemistry , Plant Stems/chemistryABSTRACT
Five new 1,3-diarylpropan-1-ols, combretol A-E (1- 5), together with one known coumarin (6) and ten known triterpenes (7-16), were isolated from Combretum yunnanense. Their structures were determined by spectroscopic investigation, including ¹H and ¹³C NMR, NOESY, HSQC, HMBC, and HRESIMS analyses. This is the first report on the occurrence of 1,3-diarylpropan-1-ols and coumarin in the Combretum genus including C. yunnanense. Also, to the best of our knowledge, 1,3-diarylpropan-1-ols are rare in nature.
Subject(s)
Combretum/chemistry , Coumarins/isolation & purification , Drugs, Chinese Herbal/isolation & purification , Triterpenes/isolation & purification , China , Coumarins/chemistry , Drugs, Chinese Herbal/chemistry , Magnetic Resonance Spectroscopy , Medicine, Chinese Traditional , Molecular Structure , Plant Components, Aerial/chemistry , Triterpenes/chemistryABSTRACT
Wnt signaling pathway is aberrantly activated in a variety of cancers, especially in colorectal cancer and small molecule antagonists of Wnt/ß-catenin signaling are attractive candidates for developing effective therapeutics. In the present study, we identified Bisleuconothine A, a bisindole alkaloid with an eburnane-aspidosperma type skeleton, as a novel and selective Wnt signaling inhibitor by using a cell-based luciferase assay system. Our study found that Bisleuconothine A down-regulated the endogenous Wnt target gene expression through promoting phosphorylation of ß-catenin and the subsequent inhibition of its nuclear translocation in HCT116 and SW480 colorectal cancer cells. In vitro, Bisleuconothine A inhibited cell proliferation through induction of apoptosis by increasing the cleavage of caspases in HCT116 and SW480 colorectal cancer cells. Moreover, in vivo, Bisleuconothine A dramatically suppressed tumor growth in HCT116 Xenograft. And further analysis showed that Bisleuconothine A suppressed the Wnt target gene expression in HCT116 Xenograft, which was associated with up-regulation of ß-catenin phosphorylation and subsequent Wnt signaling inhibition. Taken together, our study indicated that bisindole alkaloids could be included as a new chemotype of small-molecule Wnt signaling inhibitors, and have great potential to be further developed for anti-tumor agents.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Colorectal Neoplasms/drug therapy , Indole Alkaloids/pharmacology , Wnt Proteins/antagonists & inhibitors , Wnt Signaling Pathway/drug effects , beta Catenin/metabolism , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Female , HCT116 Cells , HEK293 Cells , HT29 Cells , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Phosphorylation/drug effects , RNA Interference , RNA, Small Interfering/genetics , Xenograft Model Antitumor Assays , beta Catenin/geneticsABSTRACT
OBJECTIVE: To study the diagnostic significance of computed tomography (CT) in atrial isomerism. METHOD: In one of the 2 cases of left atrial isomerism, abdominal CT scan with and without contrast enhancement were both performed, the other had plain thoraco-abdominal CT scan, and another case of right atrial isomerism received thoraco-abdominal contrast enhanced scan and thin-slice scan of the trachea. The diagnoses of all the 3 cases were surgically and pathologically confirmed. RESULT: In the CT images of the 2 cases of left atrial isomerism, some typical features were identified including bilaterally symmetric bronchi, levoversion of the heart, horizontally positioned liver, absence of hepatic segment of the inferior vena cava and dilated azygos, short pancreas and double spleen, and mirror image isomerism of the major arteries and abdominal organs. The case of right atrial isomerism had bilateral upper lobe tracheal bronchus, mirror image isomerism of the heart and abdominal organs, short pancreas, translocation of the inferior vena cava to the left of the abdominal aorta, both of which were on the left of the spine. CONCLUSIONS: CT have distinct diagnostic value in revealing thoraco-abdominal organs and major vessels, which can be crucial in the diagnosis and surgical management of patients with atrial isomerism.
Subject(s)
Heart Defects, Congenital/diagnostic imaging , Heart Defects, Congenital/diagnosis , Tomography, X-Ray Computed/methods , Adolescent , Adult , Child , Female , Heart Atria/abnormalities , Heart Defects, Congenital/surgery , Humans , Male , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
A pair of new triterpenoid epimers, kadcoccitones A (1) and B (2), together with a new biogenetically related compound kadcoccitone C (3), were isolated from Kadsura coccinea. The epimers featured an unprecedented carbon skeleton with a 6/6/5/5-fused tetracyclic ring system unit and a C(9) side chain. Their structures were determined by spectroscopic data, ECD calculation, and single-crystal X-ray diffraction. Compounds 1 and 3 showed anti-HIV-1 activity with an EC(50) value of 47.91 and 32.66 µg/mL, respectively.
Subject(s)
Anti-HIV Agents/isolation & purification , Drugs, Chinese Herbal/isolation & purification , Kadsura/chemistry , Triterpenes/isolation & purification , Anti-HIV Agents/chemistry , Anti-HIV Agents/pharmacology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , HIV-1/drug effects , Molecular Structure , Plant Stems/chemistry , Triterpenes/chemistry , Triterpenes/pharmacologyABSTRACT
Seven previously unreported daphnane-type diterpene esters named acutilobins A-G, together with 12 known ones, were isolated from EtOAc extract of Daphne acutiloba Rehd. Their structures were elucidated based on the spectroscopic data. The cytotoxic and anti-HIV-1 activities of these daphnane-type diterpene esters were evaluated through bioassays. Fourteen of these isolates exhibited definite cytotoxic activities against the five human tumor cell lines HL-60, SMMC-7721, A-549, MCF-7, and SW480. Additionally, anti-HIV-1 activities were observed in 13 daphnane-type diterpene esters, among which acutilobins A-G exhibited significant anti-HIV-1 activities with EC50 below 1.5 nM and SI over 10,000. Particularly, genkwanineVIII showed the strongest activity with EC50 0.17 nM and SI 187,010.