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1.
J Nat Prod ; 83(4): 1043-1050, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32227943

RESUMO

An extract of Galtonia regalis from the Natural Products Discovery Institute showed moderate antiplasmodial activity, with an IC50 value less than 1.25 µg/mL. The two known cholestane glycosides 1 and 2 and the five new cholestane glycosides galtonosides A-E (3-7) were isolated after bioassay-directed fractionation. The structures of the new compounds were determined by interpretation of their NMR and mass spectra. Among these compounds, galtonoside B (4) displayed the most potent antiplasmodial activity, with an IC50 value of 0.214 µM against the drug-resistant Dd2 strain of Plasmodium falciparum.


Assuntos
Antimaláricos/química , Colestanos/farmacologia , Glicosídeos/farmacologia , Asparagales/química , Colestanos/química , Colestanos/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plasmodium falciparum/química
2.
J Nat Prod ; 83(3): 569-577, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-31577436

RESUMO

In our continuing search for novel natural products with antiplasmodial activity, an extract of Aniba citrifolia was found to have good activity, with an IC50 value less than 1.25 µg/mL. After bioassay-directed fractionation, the known indolizinium alkaloid anibamine (1) and the new indolizinium alkaloid anibamine B (2) were isolated as the major bioactive constituents, with antiplasmodial IC50 values of 0.170 and 0.244 µM against the drug-resistant Dd2 strain of Plasmodium falciparum. The new coumarin anibomarin A (3), the new norneolignan anibignan A (5), and six known neolignans (7-12) were also obtained. The structures of all the isolated compounds were determined based on analyses of 1D and 2D NMR spectroscopic and mass spectrometric data, and the absolute configuration of anibignan A (5) was assigned from its ECD spectrum. Evaluation of a library of 28 anibamine analogues (13-40) indicated that quaternary charged analogues had IC50 values as low as 58 nM, while uncharged analogues were inactive or significantly less active. Assessment of the potential effects of anibamine and its analogues on the intraerythrocytic stages and morphological development of P. falciparum revealed substantial activity against ring stages for compounds with two C-10 side chains, while those with only one C-10 side chain exhibited substantial activity against trophozoite stages, suggesting different mechanisms of action.


Assuntos
Alcaloides/farmacologia , Antimaláricos/farmacologia , Lauraceae/química , Plasmodium falciparum/efeitos dos fármacos , Piridinas/farmacologia , Linhagem Celular Tumoral , Guiana , Humanos , Estrutura Molecular , Compostos Fitoquímicos/farmacologia
3.
Bioorg Med Chem Lett ; 28(20): 3368-3371, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30219526

RESUMO

Bioassay-guided fractionation of an extract of Carpha glomerata (Cyperaceae) led to the isolation of seven compounds. Compounds 1 (carphorin A), 3 (carphorin C), 4 (carphorin D), and 5 (carphabene) are new compounds, and compound 2 (8-(3″-hydroxyisoamyl)-naringenin) was isolated for the first time as a natural product. All structures were elucidated based on analyses of their HR-ESIMS and 1D and 2D NMR data. Compounds 1, 2, and 6, which have prenyl or hydroxyprenyl side chains, exhibited antiplasmodial activities with IC50 values of 5.2 ±â€¯0.6, 3.4 ±â€¯0.4, and 6.7 ±â€¯0.8 µM against the drug-resistant Dd2 strain of Plasmodium falciparum. In addition the prenylated stilbene 5 also showed good activity, with IC50 5.8 ±â€¯0.7 µM.


Assuntos
Antimaláricos/farmacologia , Cyperaceae/química , Flavanonas/farmacologia , Estilbenos/farmacologia , Antimaláricos/química , Antimaláricos/isolamento & purificação , Flavanonas/química , Flavanonas/isolamento & purificação , Plasmodium falciparum/efeitos dos fármacos , Estilbenos/química , Estilbenos/isolamento & purificação
4.
Bioorg Med Chem Lett ; 28(1): 40-42, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29162457

RESUMO

A bioassay-guided fractionation and chemical investigation of Amaryllis belladonna Steud. bulbs resulted in the isolation and identification of the new crinane alkaloid 1,4-dihydroxy-3-methoxy powellan (1), along with the 3 known crinane alkaloids 2-4 and the two lycorane alkaloids 5-6. The structures were elucidated by interpretation of combined HR-ESIMS, CD and 2D NMR spectroscopic data. Among these isolated compounds the lycorane-type alkaloid acetylcaranine (5) exhibited strong antiplasmodial activity, while compounds 3 and 4 were moderately active, and compounds 1 and 6 were inactive.


Assuntos
Alcaloides/química , Alcaloides de Amaryllidaceae/química , Antimaláricos/química , Asparagales/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Alcaloides de Amaryllidaceae/isolamento & purificação , Alcaloides de Amaryllidaceae/farmacologia , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Asparagales/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dicroísmo Circular , Humanos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Extratos Vegetais/química , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Plasmodium falciparum/efeitos dos fármacos , Espectrometria de Massas por Ionização por Electrospray
5.
J Nat Prod ; 81(5): 1260-1265, 2018 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-29738243

RESUMO

An extract of Petradoria pumila from the Natural Products Discovery Institute was found to have moderate antiplasmodial activity, with an IC50 value between 5 and 10 µg/mL. The four new diterpenoids petradoriolides A-D (1-4), the new benzotropolone petradoriolone (5), and the two known lignans 6 and 7 were isolated after bioassay-directed fractionation. The structures and stereochemistries of the new compounds were determined by interpretation of NMR spectroscopy, mass spectrometry, and ECD spectra. Among these compounds, petradoriolide C (3) displayed the most potent antiplasmodial activity, with an IC50 value of 7.3 µM.


Assuntos
Antimaláricos/química , Asteraceae/química , Biflavonoides/química , Catequina/análogos & derivados , Diterpenos/química , Antimaláricos/farmacologia , Biflavonoides/farmacologia , Catequina/química , Catequina/farmacologia , Diterpenos/farmacologia , Lignanas/química , Lignanas/farmacologia , Espectroscopia de Ressonância Magnética/métodos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plasmodium falciparum/efeitos dos fármacos
6.
J Nat Prod ; 81(3): 475-483, 2018 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-29048892

RESUMO

Nine new compounds containing either a chromane or chromene ring moiety were isolated from the monotypic plant Koeberlinia spinosa. Compounds 1-4 are chromanes with all possible E and Z isomers of the isoprenoid side chain, with compound 5 a methylated derivative of 1. Compounds 6 and 7 were assigned as diastereomeric cyclized derivatives of 2 and were probably artifacts formed during the extraction or the isolation processes. Compounds 8 and 9 were characterized as new chromenes. Structure elucidation of 1-9 was conducted via 1D and 2D NMR spectroscopic data interpretation, and absolute configurations were determined by ECD spectroscopic analysis. Compounds 2, 5, 6, and 7 had weak antiplasmodial activity, while none of the compounds exhibited antiproliferative activity. The isolation, structure elucidation, and biological evaluation of these compounds are presented.


Assuntos
Antimaláricos/farmacologia , Benzopiranos/farmacologia , Magnoliopsida/química , Plasmodium falciparum/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Espectroscopia de Ressonância Magnética/métodos
7.
J Nat Prod ; 80(7): 2037-2044, 2017 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-28654255

RESUMO

Bioassay-guided fractionation of a colon cancer growth inhibitory extract of the fungus Paraconiothyrium sp. led to the isolation of eight new versiol derivatives (1, 3-8, 10) along with two known compounds. The structures were elucidated by interpretation of combined MS and 2D NMR spectroscopic data. Compounds 8, 9, and 10 showed cell growth inhibition against COLO205 and KM12 cells, and both 8 and 9 displayed selectivity in their inhibition of melanoma cell lines in the NCI 60 one-dose test. In addition, compound 8 and the crude Paraconiothyrium sp. extract showed potent dose-dependent inhibitory effects in the five-dose NCI 60 cell line assay.


Assuntos
Ascomicetos/química , Neoplasias do Colo/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/farmacologia , Naftalenos/farmacologia , Algoritmos , Linhagem Celular Tumoral , Compostos Heterocíclicos com 3 Anéis/química , Humanos , Melanoma , Estrutura Molecular , Naftalenos/química , Ressonância Magnética Nuclear Biomolecular
8.
J Nat Prod ; 80(5): 1639-1647, 2017 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-28463001

RESUMO

A dichloromethane extract of Trichospira verticillata from the Natural Products Discovery Institute was discovered to have good antiplasmodial activity (IC50 ∼5 µg/mL). After purification by liquid-liquid partition and C18 reversed-phase HPLC, four new germacranolide-type sesquiterpenoid lactones named trichospirolides A-D (1-4) were isolated. The structures of the new compounds were elucidated by analysis of their 1D and 2D NMR and MS data. The relative and absolute configurations were assigned based on a comparison of calculated and experimental ECD and UV spectra, specific rotations, internuclear distances, and coupling constants for all possible diastereomers for each compound. Among these four compounds, the conjugated dienone 1 displayed the most potent antiplasmodial activity, with an IC50 value of 1.5 µM.


Assuntos
Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Lactonas/isolamento & purificação , Plasmodium falciparum/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Antimaláricos/química , Cromatografia Líquida de Alta Pressão , Concentração Inibidora 50 , Lactonas/química , Lactonas/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Sesquiterpenos/química , Estereoisomerismo
9.
Chem Biodivers ; 14(9)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28621040

RESUMO

Bioassay-guided fractionation of a methanol extract of Magnolia grandiflora against Plasmodium falciparum yielded two new (1 and 2) and six known (3 - 8) bioactive compounds. The structures of the new compounds were assigned by mass spectrometric and 1D- and 2D-NMR data. Known compounds were identified by comparison of 1 H-NMR and MS data with literature data. The two known neolignans 3 and 4 showed moderate antiplasmodial activity with the IC50 values of 2.8 ± 0.1 and 3.4 ± 0.1 µm, respectively. Weak antiplasmodial activity was recorded for compounds 1, 2, 5, 6, 7, and 8, with the IC50 values of 38 ± 2, 23 ± 2, 16.5 ± 0.2, 86 ± 1, 44 ± 4, and 114 ± 9 µm, respectively.


Assuntos
Antimaláricos/química , Antimaláricos/farmacologia , Lignanas/química , Lignanas/farmacologia , Magnolia/química , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/isolamento & purificação , Humanos , Lignanas/isolamento & purificação , Malária Falciparum/tratamento farmacológico , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia
10.
Bioorg Med Chem ; 24(11): 2544-8, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27112454

RESUMO

Bioassay guided fractionation of a MeOH extract of the stem bark of Syncarpia glomulifera (Myrtaceae) led to the isolation of the two new phloroglucinol derivatives (±)-rhodomyrtosone F (1) and (±)-calliviminone I (2), the three known triterpenes, betulinic acid (3), ursolic acid-3-acetate (4), and ursolic acid (5), and 1-(2,4,6-trihydroxyphenyl)-1-hexanone (6). Compound 1 exhibited strong antiplasmodial activity, while compounds 2-4 were moderately active and 5 and 6 were inactive in this assay. The structures of 1 and 2 were elucidated based on analyses of their mass spectrometric data, 1D and 2D NMR spectra, and comparison with related compounds.


Assuntos
Antimaláricos/farmacologia , Malária/tratamento farmacológico , Myrtaceae/química , Floroglucinol/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/química , Antimaláricos/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Estrutura Molecular , Testes de Sensibilidade Parasitária , Floroglucinol/química , Floroglucinol/isolamento & purificação , Casca de Planta/química , Plasmodium falciparum/crescimento & desenvolvimento , Relação Estrutura-Atividade
11.
Bioorg Med Chem ; 24(21): 5418-5422, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27624525

RESUMO

Antimalarial bioassay-guided fractionation of the swamp lily Crinum erubescens led to the isolation of four compounds with potent antiplasmodial activity. Compounds 1 and 2 were determined from their spectroscopic data to be the known pesticidal compound cripowellin A and the known pesticidal and antiproliferative compound cripowellin B. 1D and 2D-NMR techniques were used to determine the identities of 3 and 4 as the new compounds cripowellin C and D. A fifth compound was identified as the known alkaloid hippadine, which was inactive against Plasmodium falciparum. The antiplasmodial IC50 values of compounds 1-4 were determined to be 30±2, 180±20, 26±2, and 260±20nM, respectively, and their antiproliferative IC50 values against the A2780 human ovarian cancer cell line were 11.1±0.4, 16.4±0.1, 25±2, and 28±1nM.


Assuntos
Alcaloides/farmacologia , Antimaláricos/farmacologia , Crinum/química , Plasmodium falciparum/efeitos dos fármacos , Alcaloides/química , Alcaloides/isolamento & purificação , Antimaláricos/química , Antimaláricos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade
12.
J Nat Prod ; 78(10): 2440-6, 2015 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-26422131

RESUMO

Two new [(+)-cyrillins A (1) and B (2)] and four known barrigenol-like triterpenoids (3-6), along with betulinic acid and (+)-3ß-O-trans-feruloylbetulinic acid, were isolated from a sample-restricted CH2Cl2-soluble extract of the bark of Cyrilla racemiflora, collected in Dominica. The structures of the new compounds were elucidated by interpretation of their spectroscopic data, and the absolute configuration of the cyclic 1,2-diol unit of (+)-cyrillin A (1) was ascertained by analysis of the electronic circular dichroism (ECD) spectrum induced with [Mo2(OAc)4]. In the case of (+)-cyrillin B (2), which was found to contain a diangeloylated glucose residue, the structure proposed was supported by analysis of its MS(2) and MS(3) spectra. All compounds isolated were evaluated for their cytotoxicity against HT-29 human colon cancer cells, and the known compound, (+)-barringtogenol B (3), was found to be the most potent, exhibiting an IC50 value of 1.7 µM. This compound also showed inhibitory activity toward the CCD-112CoN human normal colon cell line, with an IC50 value of 5.9 µM, indicating a lack of cytotoxic selectivity.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Ericaceae/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Dominica , Ensaios de Seleção de Medicamentos Antitumorais , Glucose/análise , Células HT29 , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Triterpenos Pentacíclicos , Casca de Planta/química , Triterpenos/química , Ácido Betulínico
13.
J Nat Prod ; 78(7): 1752-5, 2015 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-26132421

RESUMO

Investigation of a DCM extract of the bark of Pleiogynium timoriense from the former Merck collection of natural product extracts for antiproliferative activity indicated that it was active with an IC50 value of 1.3 µg/mL against the A2780 ovarian cancer cell line. Bioassay-directed fractionation of this extract yielded the three new bioactive trihydroxyalkylcyclohexenones 1-3. Their structures were determined by a combination of spectroscopic and chemical methods. Compounds 1-3 exhibited submicromolar antiproliferative activity against the A2780 human ovarian cancer cell line, with IC50 values of 0.8, 0.7, and 0.8 µM, respectively.


Assuntos
Anacardiaceae/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Cicloexanonas/isolamento & purificação , Cicloexanonas/farmacologia , Antineoplásicos Fitogênicos/química , Cicloexanonas/química , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Casca de Planta/química , Tonga
14.
Planta Med ; 81(12-13): 1128-32, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26018916

RESUMO

Bioassay-guided fractionation of an EtOH extract of the roots of the plant Apoplanesia paniculata (Fabaceae) led to the isolation of the three known compounds amorphaquinone (1), pendulone (2), and melilotocarpan C (3), and the two new pterocarpans 4 and 5. Compounds 1 and 2 exhibited good antiplasmodial activity with IC50 values of 5.7 ± 1.5 and 7.0 ± 0.8 µM, respectively. Compound 3 exhibited weak antiplasmodial activity (41.8 ± 5.2 µM), while compounds 4 and 5 were inactive. Compound 6 was synthesized to confirm the structure of 5, and it showed enhanced antiplasmodial activity (15.8 ± 1.4 µM) compared to its analogues 3-5.


Assuntos
Antimaláricos/química , Fabaceae/química , Extratos Vegetais/química , Plasmodium falciparum/efeitos dos fármacos , Pterocarpanos/química , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Linhagem Celular Tumoral , Feminino , Humanos , Isoflavonas/química , Isoflavonas/isolamento & purificação , Isoflavonas/farmacologia , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Pterocarpanos/isolamento & purificação , Pterocarpanos/farmacologia , Quinonas/química , Quinonas/isolamento & purificação , Quinonas/farmacologia
15.
Bioorg Med Chem ; 22(1): 269-76, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24326280

RESUMO

Bioassay-guided separation of the South African plant Kniphofia ensifolia for antiplasmodial activity led to the isolation of two new anthraquinones, named kniphofiones A and B (3 and 4), together with three known bioactive anthraquinone monomers (1, 2 and 5), and four known bisanthraquinones (6-9). The structures of the two new compounds were elucidated based on analyses of their 1D and 2D NMR spectra and mass spectrometric data. The dimeric compounds 6 and 7 displayed the strongest antiplasmodial activity among all the isolated compounds, with IC50 values of 0.4 ± 0.1 and 0.2 ± 0.1 µM, respectively. The two new compounds displayed modest activities, with IC50 values of 26 ± 4 and 9 ± 1 µM, respectively. Due to the synthetic accessibility of the new compounds and the increased activity shown by the dimeric compounds, a structure-activity relationship study was conducted. As a result, one analogue of kniphofione B (4), the caffeic acid derivative of aloe-emodin, was found to have the highest activity among all the aloe-emodin derivatives, with an IC50 value of 1.3 ± 0.2 µM.


Assuntos
Antimaláricos/química , Antimaláricos/farmacologia , Proliferação de Células , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Relação Estrutura-Atividade
16.
J Nat Prod ; 77(3): 550-6, 2014 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-24344605

RESUMO

A new alkylated chalcone (1), a new 1,16-hexadecanediol diester (2), and eight known compounds were isolated from a dichloromethane-soluble repository extract of the leaves and twigs of Cryptocarya rubra collected in Hawaii. The structures of the new compounds were determined by interpretation of their spectroscopic data, and the absolute configurations of the two known cryptocaryanone-type flavonoid dimers, (+)-bicaryanone A (3) and (+)-chalcocaryanone C (4), were ascertained by analysis of their electronic circular dichroism and NOESY NMR spectra. All compounds isolated were evaluated against HT-29 human colon cancer cells, and, of these, (+)-cryptocaryone (5) was found to be potently cytotoxic toward this cancer cell line, with an IC50 value of 0.32 µM. This compound also exhibited glucose transport inhibitory activity when tested in a glucose uptake assay.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Chalconas/isolamento & purificação , Chalconas/farmacologia , Cryptocarya/química , Glucose/metabolismo , Antineoplásicos Fitogênicos/química , Chalconas/química , Ensaios de Seleção de Medicamentos Antitumorais , Glucose/análise , Células HT29 , Havaí , Humanos , Concentração Inibidora 50 , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química , Estereoisomerismo
17.
J Nat Prod ; 77(3): 497-502, 2014 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-24428261

RESUMO

Bacteria continue to evade existing antibiotics by acquiring resistance by various mechanisms, leading to loss of antibiotic effectiveness. To avoid an epidemic from infections of incurable drug-resistant bacteria, new antibiotics with new modes of action are desperately needed. Using a genome-wide mechanism of action-guided whole cell screening approach based on antisense Staphylococcus aureus fitness test technology, we report herein the discovery of altersolanol P (1), a new tetrahydroanthraquinone from an unknown fungus from the Hypocreales isolated from forest litter collected in Puerto Rico. The structure was elucidated by high-resolution mass spectrometry and 2D NMR spectroscopy. Relative stereochemistry was established by NOESY correlations, and absolute configuration was deduced by the application of MPA ester-based methodology. Observed (1)H and (13)C NMR shifts were well aligned with the corresponding chemical shifts predicted by DFT calculations. Altersolanol P exhibited Gram-positive antibacterial activity (MIC range 1-8 µg/mL) and inhibited the growth of Gram-negative Haemophilus influenzae (MIC 2 µg/mL). The isolation, structure elucidation, and antibacterial activity of altersolanol P are described.


Assuntos
Antraquinonas/isolamento & purificação , Antraquinonas/farmacologia , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Hypocreales/química , Staphylococcus aureus/efeitos dos fármacos , Antraquinonas/química , Antibacterianos/química , Farmacorresistência Bacteriana/efeitos dos fármacos , Haemophilus influenzae/efeitos dos fármacos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Porto Rico
18.
Diagnostics (Basel) ; 14(2)2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38248074

RESUMO

PURPOSE: Sarcopenia is considered a negative prognostic factor in patients with malignant tumors. Among other diagnostic options, computed tomography (CT), which is repeatedly performed on tumor patients, can be of further benefit. The present study aims to establish a framework for classifying the impact of sarcopenia on the prognosis of patients diagnosed with esophageal or gastric cancer. Additionally, it explores the significance of CT radiomics in both diagnostic and prognostic methodologies. MATERIALS AND METHODS: CT scans of 83 patients with esophageal or gastric cancer taken at the time of diagnosis and during a follow-up period of one year were evaluated retrospectively. A total of 330 CT scans were analyzed. Seventy three of these patients received operative tumor resection after neoadjuvant chemotherapy, and 74% of the patients were male. The mean age was 64 years (31-83 years). Three time points (t) were defined as a basis for the statistical analysis in order to structure the course of the disease: t1 = initial diagnosis, t2 = following (neoadjuvant) chemotherapy and t3 = end of the first year after surgery in the "surgery" group or end of the first year after chemotherapy. Sarcopenia was determined using the psoas muscle index (PMI). The additional analysis included the analysis of selected radiomic features of the psoas major, quadratus lumborum, and erector spinae muscles at the L3 level. Disease progression was monitored according to the response evaluation criteria in solid tumors (RECIST 1.1). CT scans and radiomics were used to assess the likelihood of tumor progression and their correlation to sarcopenia. For machine learning, the established algorithms decision tree (DT), K-nearest neighbor (KNN), and random forest (RF) were applied. To evaluate the performance of each model, a 10-fold cross-validation as well as a calculation of Accuracy and Area Under the Curve (AUC) was used. RESULTS: During the observation period of the study, there was a significant decrease in PMI. This was most evident in patients with surgical therapy in the comparison between diagnosis and after both neoadjuvant therapy and surgery (each p < 0.001). Tumor progression (PD) was not observed significantly more often in the patients with sarcopenia compared to those without sarcopenia at any time point (p = 0.277 to p = 0.465). On average, PD occurred after 271.69 ± 104.20 days. The time from initial diagnosis to PD in patients "with sarcopenia" was not significantly shorter than in patients "without sarcopenia" at any of the time points (p = 0.521 to p = 0.817). The CT radiomics of skeletal muscle could predict both sarcopenia and tumor progression, with the best results for the psoas major muscle using the RF algorithm. For the detection of sarcopenia, the Accuracy was 0.90 ± 0.03 and AUC was 0.96 ± 0.02. For the prediction of PD, the Accuracy was 0.88 ± 0.04 and the AUC was 0.93 ± 0.04. CONCLUSIONS: In the present study, the CT radiomics of skeletal muscle together with machine learning correlated with the presence of sarcopenia, and this can additionally assist in predicting disease progression. These features can be classified as promising alternatives to conventional methods, with great potential for further research and future clinical application. However, when sarcopenia was diagnosed with PMI, no significant correlation between sarcopenia and PD could be observed.

19.
J Nat Prod ; 76(5): 865-72, 2013 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-23659371

RESUMO

Investigation of the South African plant Urginea depressa Baker (Asparagaceae Juss.) for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of the six new homoisoflavonoids urgineanins A-F (1-6), the two known bufatrienolides 7 and 9, and the new bufatrienolides urginins B and C (8 and 10). Structures were elucidated based on analysis of their 1D and 2D NMR spectra, electronic circular dichroism, and mass spectrometric data. Five of the six new homoisoflavonoids had good antiproliferative activity against the A2780 ovarian cancer, A2058 melanoma, and H522-T1 human non-small-cell lung cancer cells, and urgineanin A (1) had submicromolar activity against all three cell lines. The four bufatrienolides 7-10 had strong antiproliferative activity against the same cell line, with IC50 values of 24.1, 11.2, 111, and 40.6 nM, respectively.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Drimia/química , Isoflavonas/isolamento & purificação , Isoflavonas/farmacologia , Esteroides/isolamento & purificação , Esteroides/farmacologia , Antineoplásicos Fitogênicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Concentração Inibidora 50 , Isoflavonas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Esteroides/química
20.
Tetrahedron Lett ; 54(36): 4854-4858, 2013 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-23997317

RESUMO

A new decahydronaphthalenylpropenal derivative, (+)-camerarialdehyde (1), a new tetrahydrofuran lignan, (-)-diepiolivil (2), and two known lignans were isolated from a methanol-soluble extract of the stems of Cameraria latifolia, which was obtained from a repository donated to IHVR by Merck Research Laboratories. The structures of compounds 1 and 2 were determined by interpretation of their spectroscopic data, with the absolute configuration of 1 being established by analysis of its CD spectrum. The absolute configuration of the 1,3-diol moiety of 2 was proposed from the CD spectrum induced with dimolybdenum tetraacetate in DMSO solution. All compounds isolated were evaluated against HT-29 human colon cancer cells, and compound 1 was found to show cytotoxicity toward this cell line.

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