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1.
Molecules ; 28(6)2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36985570

RESUMO

Cripowellins from Crinum erubescens are known pesticidal and have potent antiplasmodial activity. To gain mechanistic insights to this class of natural products, studies to determine the timing of action of cripowellins within the asexual intraerythrocytic cycle of Plasmodium falciparum were performed and led to the observation that this class of natural products induced reversible cytostasis in the ring stage within the first 24 h of treatment. The transcriptional program necessary for P. falciparum to progress through the asexual intraerythrocytic life cycle is well characterized. Whole transcriptome abundance analysis showed that cripowellin B "pauses" the transcriptional program necessary to progress through the intraerythrocytic life cycle coinciding with the lack of morphological progression of drug treated parasites. In addition, cripowellin B-treated parasites re-enter transcriptional progression after treatment was removed. This study highlights the use of cripowellins as chemical probes to reveal new aspects of cell cycle progression of the asexual ring stage of P. falciparum which could be leveraged for the generation of future antimalarial therapeutics.


Assuntos
Alcaloides de Amaryllidaceae , Antimaláricos , Malária Falciparum , Animais , Plasmodium falciparum , Antimaláricos/farmacologia , Antimaláricos/metabolismo , Alcaloides de Amaryllidaceae/metabolismo , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Estágios do Ciclo de Vida , Eritrócitos
2.
Molecules ; 29(1)2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38202761

RESUMO

Dolichols are isoprenoid end-products of the mevalonate and 2C-methyl-D-erythritol-4-phosphate pathways. The synthesis of dolichols is initiated with the addition of several molecules of isopentenyl diphosphate to farnesyl diphosphate. This reaction is catalyzed by a cis-prenyltransferase and leads to the formation of polyprenyl diphosphate. Subsequent steps involve the dephosphorylation and reduction of the α-isoprene unit by a polyprenol reductase, resulting in the generation of dolichol. The size of the dolichol varies, depending on the number of isoprene units incorporated. In eukaryotes, dolichols are synthesized as a mixture of four or more different lengths. Their biosynthesis is predicted to occur in the endoplasmic reticulum, where dolichols play an essential role in protein glycosylation. In this study, we have developed a selection of aptamers targeting dolichols and enhanced their specificity by incorporating fatty acids for negative selection. One aptamer showed high enrichment and specificity for linear polyisoprenoids containing at least one oxygen atom, such as an alcohol or aldehyde, in the α-isoprene unit. The selected aptamer proved to be a valuable tool for the subcellular localization of polyisoprenoids in the malaria parasite. To the best of our knowledge, this is the first time that polyisoprenoids have been localized within a cell using aptamer-based imaging techniques.


Assuntos
Butadienos , Hemiterpenos , Malária , Parasitos , Animais , Diagnóstico por Imagem , Dolicóis
3.
Org Biomol Chem ; 20(45): 9000-9009, 2022 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-36330968

RESUMO

Seventeen new cephalotane-type diterpenoids, fortalides A-Q (1-17), along with five known analogues, were isolated from the seeds of Cephalotaxus fortunei var. alpina. Their structures were determined by extensive spectroscopic methods, as well as electronic circular dichroism (ECD) and X-ray crystallographic data analyses. Some isolates exhibited unusual structural features that were first found in cephalotane-type diterpenoids, such as the occurrence of the 7-oxabicyclo[4.1.1]octane moiety in 14 and 15 and the cis-arrangement of 3-OH and Me-19 in 9. Besides, the antiplasmodial activity of these compounds was evaluated in this study.


Assuntos
Cephalotaxus , Diterpenos , Cephalotaxus/química , Estrutura Molecular , Diterpenos/farmacologia , Diterpenos/química , Dicroísmo Circular , Cristalografia por Raios X
4.
Genet Med ; 23(7): 1305-1314, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33731878

RESUMO

PURPOSE: Variants in NUS1 are associated with a congenital disorder of glycosylation, developmental and epileptic encephalopathies, and are possible contributors to Parkinson disease pathogenesis. How the diverse functions of the NUS1-encoded Nogo B receptor (NgBR) relate to these different phenotypes is largely unknown. We present three patients with de novo heterozygous variants in NUS1 that cause a complex movement disorder, define pathogenic mechanisms in cells and zebrafish, and identify possible therapy. METHODS: Comprehensive functional studies were performed using patient fibroblasts, and a zebrafish model mimicking NUS1 haploinsufficiency. RESULTS: We show that de novo NUS1 variants reduce NgBR and Niemann-Pick type C2 (NPC2) protein amount, impair dolichol biosynthesis, and cause lysosomal cholesterol accumulation. Reducing nus1 expression 50% in zebrafish embryos causes abnormal swim behaviors, cholesterol accumulation in the nervous system, and impaired turnover of lysosomal membrane proteins. Reduction of cholesterol buildup with 2-hydroxypropyl-ß-cyclodextrin significantly alleviates lysosomal proteolysis and motility defects. CONCLUSION: Our results demonstrate that these NUS1 variants cause multiple lysosomal phenotypes in cells. We show that the movement deficits associated with nus1 reduction in zebrafish arise in part from defective efflux of cholesterol from lysosomes, suggesting that treatments targeting cholesterol accumulation could be therapeutic.


Assuntos
Haploinsuficiência , Doença de Niemann-Pick Tipo C , Animais , Linhagem Celular , Colesterol , Haploinsuficiência/genética , Humanos , Lisossomos , Fenótipo , Receptores de Superfície Celular/genética , Peixe-Zebra/genética
5.
Bioorg Med Chem Lett ; 30(22): 127520, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-32898696

RESUMO

The antimalarial candidate MMV008138 (1a) is of particular interest because its target enzyme (IspD) is absent in human. To achieve higher potency, and to probe for steric demand, a series of analogs of 1a were prepared that featured methyl-substitution of the B- and C-rings, as well as ring-chain transformations. X-ray crystallography, NMR spectroscopy and calculation were used to study the effects of these modifications on the conformation of the C-ring and orientation of the D-ring. Unfortunately, all the B- and C-ring analogs explored lost in vitro antimalarial activity. The possible role of steric effects and conformational changes on target engagement are discussed.


Assuntos
Antimaláricos/química , Carbolinas/química , Ácidos Pipecólicos/química , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/síntese química , Carbolinas/síntese química , Relação Dose-Resposta a Droga , Conformação Molecular , Testes de Sensibilidade Parasitária , Ácidos Pipecólicos/síntese química , Plasmodium falciparum/crescimento & desenvolvimento , Relação Estrutura-Atividade
6.
J Nat Prod ; 83(6): 1751-1765, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32468815

RESUMO

Eighteen new limonoids, including eight methyl angolensates (1-8) and 10 cipadesins (9-18), were isolated from the leaves of Cipadessa baccifera. Their structures were characterized by means of spectroscopic data analyses, single-crystal X-ray diffraction, and quantum chemistry computational methods. The C-6 configurations in those compounds possessing a C-6 hydroxy group were all assigned as S regardless of the magnitude of J5,6, and the C-2' configuration in those bearing a 2-methylbutyryl residue was defined by single-crystal X-ray diffraction and NMR data. Compounds 1, 5, 6, 7, 11, and 12 showed moderate antimalarial activities with IC50 values ranging from 12 to 28 µM.


Assuntos
Limoninas/química , Meliaceae/química , Animais , Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/química , Limoninas/farmacologia , Espectroscopia de Ressonância Magnética , Conformação Molecular , Estrutura Molecular , Folhas de Planta/química , Plasmodium falciparum/efeitos dos fármacos , Espectrometria de Massas por Ionização por Electrospray , Difração de Raios X
7.
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
8.
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
9.
Bioorg Chem ; 100: 103925, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32438132

RESUMO

Vitex rotundifolia is an important medicinal plant frequently employed in traditional medicines for the treatment of various ailments. Although this plant species has been under exploration for its constituents by various research groups including our own group, no reports were found regarding the antimalarial potential of this plant or of its purified phytochemicals. Phytochemical investigation of this plant yielded three new (1-3) and five known (4-8) diterpenoids. These compounds were purified by modern chromatographic techniques and their structures were determined by advanced spectroscopic techniques such as nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). The in vitro antiplasmodial activities were encouraging, as compounds 2, 6, and 8 were found to have significant IC50 values of 1.2, 1.3 and 11.0 µM, respectively against Plasmodium falciparum.


Assuntos
Antimaláricos/química , Antimaláricos/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Vitex/química , Antimaláricos/isolamento & purificação , Diterpenos/isolamento & purificação , Humanos , Malária Falciparum/tratamento farmacológico , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química
10.
Chem Pharm Bull (Tokyo) ; 68(7): 671-674, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612002

RESUMO

Chromatographic separation of the acetone extracts from the twigs and barks of Artocarpus lakoocha led to the isolation of the one new flavanone, lakoochanone (1), together with eleven known compounds (2-12). Lakoochanone (1) and moracin C (4) exhibited weak antiplasmodial activity against Plasmodium falciparum Dd2 with IC50 values of 36.7 and 33.9 µM, respectively. Moreover, moracin C (4) and sanggenofuran B (5) showed cytotoxic activity against A2780 cell line with the respective IC50 values of 15.0 and 57.1 µM. In addition, cyclocommunin (7) displayed strong antimycobacterial activity against Mycobacterium tuberculosis H37Ra with the minimum inhibitory concentration (MIC) value of 12.3 µM.


Assuntos
Antiprotozoários/farmacologia , Antituberculosos/farmacologia , Artocarpus/química , Flavanonas/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Antituberculosos/química , Antituberculosos/isolamento & purificação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Flavanonas/química , Flavanonas/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Testes de Sensibilidade Parasitária , Casca de Planta/química , Caules de Planta/química , Relação Estrutura-Atividade
11.
J Nat Prod ; 82(3): 431-439, 2019 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-30354100

RESUMO

Garcinia dauphinensis is a previously uninvestigated endemic plant species of Madagascar. The new phloroglucinols dauphinols A-F and 3'-methylhyperjovoinol B (1-7) and six known phloroglucinols (8-13) together with tocotrienol 14 and the three triterpenoids 15-17 were isolated from an ethanolic extract of G. dauphinensis roots using various chromatographic techniques. The structures of the isolated compounds were elucidated by NMR, MS, optical rotation, and ECD data. Theoretical ECD spectra and specific rotations for 2 were calculated and compared to experimental data in order to assign its absolute configuration. Among the compounds tested, 1 showed the most promising growth inhibitory activity against A2870 ovarian cancer cells, with IC50 = 4.5 ± 0.9 µM, while 2 had good antiplasmodial activity against the Dd2 drug-resistant strain of Plasmodium falciparum, with IC50 = 0.8 ± 0.1 µM.


Assuntos
Proliferação de Células/efeitos dos fármacos , Floroglucinol/farmacologia , Raízes de Plantas/química , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/química , Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Etanol/química , Garcinia/química , Humanos , Estrutura Molecular , Floroglucinol/química , Floroglucinol/isolamento & purificação , Extratos Vegetais/química
12.
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
13.
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
14.
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
15.
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
16.
Bioorg Med Chem ; 25(15): 4203-4211, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28648491

RESUMO

Antiplasmodial bioassay guided fractionation of a Madagascar collection of Crinum firmifolium led to the isolation of seven compounds. Five of the seven compounds were determined to be 2-alkylquinolin-4(1H)-ones with varying side chains. Compounds 1 and 4 were determined to be known compounds with reported antiplasmodial activities, while 5 was believed to be a new branched 2-alkylquinolin-4(1H)-one, however, it was isolated in limited quantities and in admixture and therefore was synthesized to confirm its structure as a new antiplasmodial compound. Along with 5, two other new and branched compounds 6 and 7 were synthesized as well. Accompanying the five quinolones were two known compounds 2 and 3 which are inactive against Plasmodium falciparum. The isolation, structure elucidation, total synthesis, and biological evaluation of these compounds are discussed in this article.


Assuntos
Antimaláricos/química , Antimaláricos/isolamento & purificação , Crinum/química , Plasmodium falciparum/efeitos dos fármacos , Quinolonas/química , Quinolonas/isolamento & purificação , Antimaláricos/síntese química , Espectrometria de Massas , Espectroscopia de Prótons por Ressonância Magnética , Quinolonas/síntese química , Espectrofotometria Ultravioleta
17.
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
18.
J Nat Prod ; 80(1): 96-107, 2017 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-27997206

RESUMO

Inspired by the discovery of the antimalarial drug artemisinin from a traditional Chinese medicine (TCM), a natural product library of 44 lindenane-type sesquiterpenoids was assessed for activities against the Dd2 chloroquine-resistant strain of the malaria parasite Plasmodium falciparum. These compounds were mainly isolated from plants of the Chloranthus genus, many species of which are named "Sikuaiwa" in TCM and have long been used to treat malaria. The compounds consisted of 41 sesquiterpenoid dimers and three monomers, including the 12 new dimers 1-12 isolated from Chloranthus fortunei. The results showed that 16 dimers exhibited potent antiplasmodial activities (<100 nM); in particular, compounds 1, 14, and 19 exhibited low nanomolar activities with IC50 values ranging from 1 to 7 nM, which is comparable to the potency of artemisinin, and selectivity index values toward mammalian cells greater than 500. A comprehensive structure-activity relationship study indicated that three functional groups are essential and two motifs can be modified.


Assuntos
Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Artemisininas/química , Cloroquina/farmacologia , Magnoliopsida/química , Plantas Medicinais/química , Plasmodium falciparum/efeitos dos fármacos , Animais , Antimaláricos/química , Cloroquina/química , Concentração Inibidora 50 , Estrutura Molecular , Relação Estrutura-Atividade
19.
Chem Biodivers ; 14(12)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28817228

RESUMO

An extract of Malleastrum sp. (Meliaceae) collected in Madagascar by the Madagascar International Cooperative Biodiversity Group was found to have antimalarial activity, with an IC50 value between 2.5 and 5 µg ml-1 . After purification by liquid-liquid partition, chromatography on a Diaion open column, C18 SPE and C18 reversed phase HPLC, the new butanolide, malleastrumolide A, was isolated. The structure of malleastrumolide A was determined by mass spectrometry, NMR, and ECD. The double bond position was determined by cross-metathesis and mass spectrometry. The compound has antiproliferative activity against the A2780 ovarian cancer cell line with an IC50 value of 17.4 µm and antiplasmodial activity against the drug-resistant Dd2 strain of Plasmodium falciparum with an IC50 value of 2.74 µm.


Assuntos
4-Butirolactona/análogos & derivados , Antimaláricos/química , Meliaceae/química , 4-Butirolactona/química , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/toxicidade , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dicroísmo Circular , Humanos , Concentração Inibidora 50 , Extração Líquido-Líquido , Madagáscar , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Meliaceae/metabolismo , Conformação Molecular , Extratos Vegetais/química , Plasmodium falciparum/efeitos dos fármacos
20.
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
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