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1.
Phytochemistry ; 171: 112231, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901473

RESUMO

Daphne giraldii Nitsche., a member of the genus Daphne (Thymelaeaceae), is a deciduous shrub with mild toxicity. Its rhizome bark, generally called 'Zushima' in Chinese, has many medicinal folkloric uses and good therapeutic effects. Previous studies investigating the chemical constituents and pharmacological activities of D. giraldii have focused on several major classes of compounds, such as coumarins, lignans and flavonoids, especially the interesting enantiomeric flavans. Extracts and pure compounds of D. giraldii were found to possess anti-inflammatory, anti-nociceptive, cytotoxicity, antimalarial, immunomodulating, sedative and hypnotic effects. They have also been reported to influence the cardiovascular functions and blood activities. This comprehensive review will describe the advances in the phytochemistry, pharmacology, medicinal uses and clinical applications of D. giraldii and its formulations covering the literature published from 1970 to 2018. Almost half of the reviewed studies were originally published in non-English languages (mainly in Chinese). Collectively, the aim of this article is to open new avenues for further in-depth pharmacological studies on D. giraldii.


Assuntos
Compostos Fitoquímicos/farmacologia , Thymelaeaceae/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/farmacologia , Fármacos Antiobesidade/química , Fármacos Antiobesidade/isolamento & purificação , Fármacos Antiobesidade/farmacologia , Antimaláricos/química , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Humanos , Hipnóticos e Sedativos/química , Hipnóticos e Sedativos/isolamento & purificação , Hipnóticos e Sedativos/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação
2.
Planta Med ; 86(1): 19-25, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31663109

RESUMO

Three new (1: -3: ) and 2 known (4: -5: ) bis-indole alkaloids were identified from the bark of Flindersia pimenteliana (Rutaceae). The structures of 1: -3: were elucidated on the basis of their (+)-HRESESIMS and 2D NMR spectroscopic data. Antiplasmodial activity for 1: -3: against chloroquine sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum is also reported, with IC50 values ranging from 0.96 to 2.41 µg/mL. These results expand our knowledge of the structure-activity relationships of potently antiplasmodial isoborreverine-type alkaloids, the bioactivity of which have recently attracted significant attention in the literature.


Assuntos
Antimaláricos/isolamento & purificação , Alcaloides Indólicos/isolamento & purificação , Rutaceae/química , Antimaláricos/química , Antimaláricos/farmacologia , Células HEK293 , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Casca de Planta/química , Plasmodium falciparum/efeitos dos fármacos , Relação Estrutura-Atividade
3.
J Ethnopharmacol ; 247: 112203, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31472271

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Combretum racemosum showed activity in previous ethnopharmacological investigations of some Combretum species used in malaria treatment in parts of West Africa. AIM OF THE STUDY: This study aimed at confirming the antimalarial potential of this plant by an activity-guided isolation of its active principles. MATERIALS AND METHODS: A crude methanolic leaf extract of Combretum racemosum and fractions thereof obtained by partition with chloroform and n-butanol were investigated for antiplasmodial activity against chloroquine-sensitive (D10) and chloroquine-resistant (W2) strains of Plasmodium falciparum. Repeated chromatographic separations were conducted on the chloroform fraction to isolate bioactive compounds for further tests on antiplasmodial activity. The characterization of the isolated substances was performed by applying NMR- and MS-techniques (ESI-MS, HR-ESIMS, 1D and 2D NMR). RESULTS: The chloroform fraction (D10: IC50 = 33.8 ±â€¯1.5 µg/mL and W2: IC50 = 27.8 ±â€¯2.9 µg/mL) exhibited better antiplasmodial activity than the n-butanol fraction (D10: IC50 = 78.1 ±â€¯7.3 µg/mL and W2: IC50 = 78 ±â€¯15 µg/mL) as well as the methanolic raw extract (D10: IC50 = 64.2 ±â€¯2.7 µg/mL and W2: IC50 = 65.8 ±â€¯14.9 µg/mL). Thus, the focus of the phytochemical investigation was laid on the chloroform fraction, which led to the identification of four ursane-type (19α-hydroxyasiatic acid (1), 6ß,23-dihydroxytormentic acid (4), madecassic acid (8), nigaichigoside F1 (10)) and four oleanane-type (arjungenin (2), combregenin (5), terminolic acid (7), arjunglucoside I (11)) triterpenes, as well as abscisic acid (9). Compounds 1 and 2, 4 and 5, 7 and 8 as well as 10 and 11 were isolated as isomeric mixtures in fractions CR-A, CR-C, CR-E and CR-H, respectively. All isolated compounds and mixtures exhibited moderate to low activity, with madecassic acid being most active (D10: IC50 = 28 ±â€¯12 µg/mL and W2: IC50 = 17.2 ±â€¯4.3 µg/mL). CONCLUSION: This paper reports for the first time antiplasmodial principles from C. racemosum and thereby gives reason to the traditional use of the plant.


Assuntos
Antimaláricos/farmacologia , Combretum/química , Extratos Vegetais/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Triterpenos/farmacologia , África Ocidental , Animais , Antimaláricos/isolamento & purificação , Antimaláricos/uso terapêutico , Etnofarmacologia , Humanos , Malária/tratamento farmacológico , Malária/parasitologia , Medicina Tradicional Africana/métodos , Metanol/química , Testes de Sensibilidade Parasitária , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Triterpenos/isolamento & purificação , Triterpenos/uso terapêutico
4.
BMC Complement Altern Med ; 19(1): 171, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296214

RESUMO

BACKGROUND: Drug resistance poses a challenge to malaria control measures. This calls for discovery & development of new chemotherapeutic agents. This study therefore was initiated to investigate the antimalarial activity of Olea europaea against Plasmodium berghei infected mice and to further ascertain in which fraction (s) the constituents responsible for anti-malarial activity are concentrated. METHODS: The leaves of Olea europaea were extracted by maceration using 80% methanol and the crude extract was then successively fractionated with solvents of differing polarity (chloroform, n-butanol and water). The anti-malarial activity of various doses of the extract and fractions (200, 400 and 600 mg/kg) was evaluated using chemo-suppressive, curative, and repository tests. Parameters, including parasitemia, rectal temperature, body weight, and packed cell volume were determined to establish the activity. RESULTS: The acute oral toxicity test result revealed that the LD50 values of the extract and fractions were greater than 2000 mg/kg in mice. The crude extract significantly reduced parasitemia (p < 0.001) and prolonged survival time (p < 0.001), in a dose-dependent manner, in all tests, as compared to the negative control group. Higher parasitemia suppression (58%) was achieved with the larger dose (600 mg/kg) in the 4-day suppressive test, suggesting that the crude extract has largely a chemo-suppressive activity. Parasitemia was significantly reduced (p < 0.001) by all fractions in all doses used when compared to the negative controls, with the rank order of n-butanol (51%) > chloroform>aqueous (21%) fractions. Larger (600 mg/kg) and middle (400 mg/kg) doses of the crude extract as well as the fractions ameliorated all the other parameters in a consistent manner, with the crude being more active than the fractions. Preliminary phytochemical analysis revealed the presence of secondary metabolites that were differentially distributed in the fractions. CONCLUSION: The findings collectively indicate that the plant is endowed with antimalarial activity, the activity being more in the crude extract than the fractions, owing to the presence of secondary metabolites that act independently or in synergy. The varying degree of antimalarial activity in the fractions suggests that non-polar and medium polar principles could be responsible for the observed activity.


Assuntos
Antimaláricos/farmacologia , Malária/tratamento farmacológico , Olea/química , Extratos Vegetais/farmacologia , Plasmodium berghei/efeitos dos fármacos , Animais , Antimaláricos/isolamento & purificação , Antimaláricos/toxicidade , Feminino , Malária/parasitologia , Masculino , Camundongos , Parasitemia/tratamento farmacológico , Fitoterapia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Folhas de Planta/química , Solventes , Testes de Toxicidade
5.
Fitoterapia ; 137: 104188, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31158428

RESUMO

Repeated chromatographic purifications of aerial parts of the Tunisian plant Daucus virgatus led to the isolation of four new germacranolides, named daucovirgolides I-L (2-5), along with the Plasmodium transmission-blocking agent daucovirgolide G. The chemical structures of the new compounds were defined as mono- or di-angeloylated germacrane-type sesquiterpenoids by spectroscopic (mainly 1D and 2D NMR) and spectrometric methods (ESIMS). The low potency exhibited by daucovirgolides I-L further supports the observation that strict structural requirements do exist for the Plasmodium transmission blocking activity in the daucovirgolide series. In particular, the endocyclic double bond system seems to be crucial for bioactivity.


Assuntos
Antimaláricos/farmacologia , Apiaceae/química , Plasmodium berghei/efeitos dos fármacos , Sesquiterpenos de Germacrano/farmacologia , Antimaláricos/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/química , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/isolamento & purificação , Tunísia
6.
Chem Biodivers ; 16(7): e1900141, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31087758

RESUMO

Bioguided fractionation of Xylopia sericea antiplasmodial dichloromethane leaves extract led to the isolation of (-)-7-oxo-ent-kaur-16-en-19-oic acid (C20 H28 O3 ) that was identified by a combination of 1D and 2D NMR experiments (COSY, HMBC, HSQC, HSQC-TOCSY, HSQC-NOESY and NOESY) and by X-ray crystallography. A feature to be pointed out is its (4R) configuration that was inferred from the NOE experiments (HSQC-NOESY and NOESY) and X-ray crystallography. In vitro evaluation of this rare diterpene acid against the chloroquine-resistant strain Plasmodium falciparum W2 by the PfLDH method showed it disclosed a low antiplasmodial activity and was not cytotoxic to HepG2 cells (CC50 862.6±6.7 µm) by the MTT assay. The unequivocal NMR signals assignments, the X-ray crystallographic structure, the assessment to the bioactivities and the occurrence this diterpene in X. sericea are reported here for the first time.


Assuntos
Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Diterpenos de Caurano/farmacologia , Diterpenos/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Plasmodium falciparum/efeitos dos fármacos , Xylopia/química , Antimaláricos/química , Antimaláricos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos de Caurano/química , Diterpenos de Caurano/isolamento & purificação , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-Atividade
7.
Mar Drugs ; 17(5)2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31035452

RESUMO

Rare actinomycetes are prolific in the marine environment; however, knowledge about their diversity, distribution and biochemistry is limited. Marine rare actinomycetes represent a rather untapped source of chemically diverse secondary metabolites and novel bioactive compounds. In this review, we aim to summarize the present knowledge on the isolation, diversity, distribution and natural product discovery of marine rare actinomycetes reported from mid-2013 to 2017. A total of 97 new species, representing 9 novel genera and belonging to 27 families of marine rare actinomycetes have been reported, with the highest numbers of novel isolates from the families Pseudonocardiaceae, Demequinaceae, Micromonosporaceae and Nocardioidaceae. Additionally, this study reviewed 167 new bioactive compounds produced by 58 different rare actinomycete species representing 24 genera. Most of the compounds produced by the marine rare actinomycetes present antibacterial, antifungal, antiparasitic, anticancer or antimalarial activities. The highest numbers of natural products were derived from the genera Nocardiopsis, Micromonospora, Salinispora and Pseudonocardia. Members of the genus Micromonospora were revealed to be the richest source of chemically diverse and unique bioactive natural products.


Assuntos
Actinobacteria/química , Organismos Aquáticos/química , Produtos Biológicos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Antimaláricos/química , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Antiparasitários/química , Antiparasitários/isolamento & purificação , Antiparasitários/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação
8.
Fitoterapia ; 134: 429-434, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30898727

RESUMO

Six new polyketide-derived oxaphenalenone dimers, talaromycesone C (1) and macrosporusones A-E (2-6), together with eight known analogs, were isolated from the mycelium of the fungus Talaromyces macrosporus KKU-1NK8. Their structures were established based on their spectroscopic data and MS. The absolute configurations of new compounds 1-6 were determined by ECD analyses. Compounds 3 and 8 exhibited antimalarial activity against Plasmodium falciparum. Compound 3 showed activity against NCI-H187 cells, while compound 8 displayed activity against KB, MCF-7 and NCI-H187 cell lines. In addition, compound 11 showed antibacterial activity against Bacillus cereus, Staphylococcus aureus and MRSA.


Assuntos
Antibacterianos/farmacologia , Antimaláricos/farmacologia , Talaromyces/química , Animais , Antibacterianos/isolamento & purificação , Antimaláricos/isolamento & purificação , Bacillus cereus/efeitos dos fármacos , Linhagem Celular Tumoral , Florestas , Humanos , Estrutura Molecular , Plasmodium falciparum/efeitos dos fármacos , Microbiologia do Solo , Staphylococcus aureus/efeitos dos fármacos , Tailândia , Células Vero
9.
Planta Med ; 85(8): 637-647, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30909312

RESUMO

The spread of malaria is thought to have followed human expansion out of Africa some 60 - 80 thousand years ago. With its prevalence in pantropical countries of the world and epicenter localized in Africa, malaria is now considered an unnecessary burden to overworked and under-resourced healthcare structures. Plants have long afforded a fertile hunting ground for the search and identification of structurally diverse antimalarial agents, such as quinine and artemisinin. This survey examines the antiparasitic properties of the family Amaryllidaceae via the antiplasmodial activities demonstrated for its lycorane alkaloid principles. Of these, 24 were natural compounds identified in 20 species from 11 genera of the Amaryllidaceae family, whilst the remaining 28 were synthetically derived entities based on the lycorane skeleton. These were screened against ten different strains of the malarial parasite Plasmodium falciparum, wherein the parent compound lycorine was shown to be the most potent with an IC50 of 0.029 µg/mL in the FCR-3 strain seen to be the best. Structure-activity relationship studies revealed that good activities were detectable across both the natural compounds as well as the synthetically accessed derivatives. Such studies also highlighted that there are several inherent structural features that define the lycorane alkaloid antiplasmodial pharmacophore, such as the nature of its ring systems and properties of its substituents. Mechanistically, a limited number of studies confirmed that lycorane alkaloids manifest their action by targeting enzymes associated with the plasmodial FAS-II biosynthetic pathways. Overall, these alkaloids have provided useful, convenient, and accessible scaffolds for antimalarial-based drug discovery.


Assuntos
Alcaloides de Amaryllidaceae/farmacologia , Amaryllidaceae/química , Antimaláricos/farmacologia , Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/isolamento & purificação , Animais , Antimaláricos/química , Antimaláricos/isolamento & purificação , Humanos , Plasmodium falciparum/efeitos dos fármacos , Relação Estrutura-Atividade
10.
Mar Drugs ; 17(3)2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30875899

RESUMO

Chemical study of the CH2Cl2-MeOH (1:1) extract of the sponge Fascaplysinopsis reticulata collected in Mayotte highlighted three new tryptophan derived alkaloids, 6,6'-bis-(debromo)-gelliusine F (1), 6-bromo-8,1'-dihydro-isoplysin A (2) and 5,6-dibromo-8,1'-dihydro-isoplysin A (3), along with the synthetically known 8-oxo-tryptamine (4) and the three known molecules from the same family, tryptamine (5), (E)-6-bromo-2'-demethyl-3'-N-methylaplysinopsin (6) and (Z)-6-bromo-2'-demethyl-3'-N-methylaplysinopsin (7). Their structures were elucidated by 1D and 2D NMR spectra and HRESIMS data. All compounds were evaluated for their antimicrobial and their antiplasmodial activities. Regarding antimicrobial activities, the best compounds are (2) and (3), with minimum inhibitory concentration (MIC) of 0.01 and 1 µg/mL, respectively, towards Vibrio natrigens, and (5), with MIC values of 1 µg/mL towards Vibrio carchariae. In addition the known 8-oxo-tryptamine (4) and the mixture of the (E)-6-bromo-2'-demethyl-3'-N-methylaplysinopsin (6) and (Z)-6-bromo-2'-demethyl-3'-N-methylaplysinopsin (7) showed moderate antiplasmodial activity against Plasmodium falciparum with IC50 values of 8.8 and 8.0 µg/mL, respectively.


Assuntos
Anti-Infecciosos/farmacologia , Antimaláricos/farmacologia , Poríferos/química , Triptaminas/química , Triptaminas/farmacologia , Alcaloides/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Antimaláricos/química , Antimaláricos/isolamento & purificação , Concentração Inibidora 50 , Biologia Marinha , Plasmodium falciparum/efeitos dos fármacos , Triptaminas/isolamento & purificação , Vibrio/efeitos dos fármacos
11.
J Ethnopharmacol ; 235: 111-121, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-30738118

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Annona muricata (Annonaceae) is a commonly used medicinal plants in Cameroonian traditional medicines to treat various diseases including malaria. Previous studies have shown that extracts from this plant have antiplasmodial activity. AIM OF THE STUDY: This study aimed to explore the endophyic fungi associated with some parts of this plant for their ability to produce antiplasmodial metabolites. MATERIALS AND METHODS: One hundred and fifty-two endophytic fungi isolated from twelve different organs of A. muricata were cultured and the ethyl acetate extracts of conditioned media screened for antiplasmodial activity using the 96-well microtiter plate format SYBR green florescence assay against Chloroquine-sensitive Pf3D7 and Chloroquine-resistant PfINDO/PfDd2 strains of Plasmodium falciparum. RESULTS: Twenty-seven (17.76%) of fungi tested were found to completely inhibit the growth of Plasmodium parasites at 10 µg/mL. The 5.8S rDNA sequencing data revealed the strongly active (IC50 < 2 µg/mL against at least 2 P. falciparum strains) isolates to be Trichoderma afroharzianum AMrb7, Penicillium citrinum AMrb11, Neocosmospora rubicola AMb22, Penicillium tropicum AMb3, Penicillium citrinum AMrb23, Aspergillus versicolor AMb7, and Fusarium sp AMst1. Of these, the extracts from Penicillium citrinum AMrb11 (IC50 0.84-0.93 µg/mL) and Neocosmospora rubicola AMb22 (IC50 0.39-1.92 µg/mL) showed the highest promise against all three plasmodial strains with selectivity indices ranging from 34.71 to 180.97. Dynamic head space GC-MS analysis of ethyl acetate extracts of promising fungi revealed broad-spectrum antimicrobial compounds such as Penicidin, Aromadendrene, Ethyl p-methoxycinnamate, 2-Coumaranone and 2-Methyl resorcinol. CONCLUSION: These results have opened new avenues for discovery of novel antimalarial lead compounds from endophytic fungi associated with Annona muricata - a medicinally important plant.


Assuntos
Annona/microbiologia , Antimaláricos/farmacologia , Fungos/isolamento & purificação , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/administração & dosagem , Antimaláricos/isolamento & purificação , Camarões , Cloroquina/farmacologia , Descoberta de Drogas/métodos , Endófitos/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas/métodos , Concentração Inibidora 50 , Medicina Tradicional Africana/métodos
12.
Fitoterapia ; 134: 305-313, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30763721

RESUMO

Malaria is prevalent in tropical and subtropical regions of the globe. With over 200 million cases reported annually, particularly in sub-Saharan Africa, it is an unnecessary burden to already overworked and ailing healthcare structures. Traditional medicine (TM) remains vibrant in most of these regions wherein plants often serve as the first line of defense against malaria. Given this fact as well as the successes elsewhere of therapies such as Artemisia annua emanating from evidence-based TM, interest in plants as a source of new antimalarial drugs has been rejuvenated. The bulbous plant family Amaryllidaceae is recognized for its structurally-diverse alkaloid constituents which exhibit interesting biological properties. This review focuses on the in vitro activities demonstrated by its crinane alkaloids against various strains of the malaria-causing parasite Plasmodium falciparum. The survey embraces the twelve genera of the Amaryllidaceae whose nineteen representative species have been examined for antiplasmodial crinane alkaloid principles. A total of seventy-two compounds were screened against nine strains of P. falciparum, with the α-crinanes reflecting better overall activities than their corresponding ß-crinane subgroup congeners. In terms of potency, an ED50 of 0.14 µg/mL (for augustine in the D-6 strain) and IC50 of 0.35 µg/mL (for haemanthidine in the K1 strain) were the lowest activity indices observed. Structure-activity relationship studies afforded useful insight on the antiplasmodial pharmacophore and the features supporting its efficacy. Overall, crinane alkaloids have provided a useful platform for the study of antiplasmodial effects, not only in terms of potency but also in terms of structural diversity.


Assuntos
Alcaloides de Amaryllidaceae/farmacologia , Amaryllidaceae/química , Antimaláricos/farmacologia , Amaryllidaceae/classificação , Alcaloides de Amaryllidaceae/isolamento & purificação , Antimaláricos/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Plasmodium falciparum/efeitos dos fármacos
13.
Malar J ; 18(1): 8, 2019 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30642330

RESUMO

BACKGROUND: The erythrocytic stage of Plasmodium falciparum parasites in humans is clinically important, as the parasites at this growth stage causes malarial symptoms. Most of the currently available anti-malarial drugs target this stage, but the emergence and spread of parasites resistant to anti-malarial drugs are a major challenge to global eradication efforts; therefore, the development of novel medicines is urgently required. In this study, the in vitro anti-malarial activity of five current anti-malarial drugs (artemisinin, atovaquone, chloroquine, mefloquine, and pyrimethamine) and 400 compounds from the Pathogen Box provided by the Medicines for Malaria Venture on P. falciparum parasites was characterized using the XN-30 analyzer. Furthermore, the outcomes obtained using the analyser were classified according to the parasitaemias of total and each developmental stages. RESULTS: The growth inhibition rate and the half-maximal (50%) inhibitory concentration (IC50) of the five current anti-malarial drugs were calculated from the parasitaemia detected using the XN-30 analyzer. Respective strains and drugs presented strongly fitted sigmoidal curves, and the median SD at all tested concentrations was 1.6, suggesting that the variation in values measured with the analyser was acceptably low for the comparison of drug efficacy. Furthermore, the anti-malarial activity of the 400 compounds from the Pathogen Box was tested, and 141 drugs were found to be effective. In addition, the efficacy was classified into 4 types (Type I, parasites were arrested or killed without DNA replication; Type II, parasites were arrested or killed similar to Type I, and the parasitaemia was apparently decreased; Type III, parasites progressed to trophozoite without sufficient DNA replication; and Type IV, parasites were arrested at late trophozoite or schizont after DNA replication). CONCLUSION: The current study demonstrates that the XN-30 analyzer objectively, reproducibly, and easily evaluated and characterized the anti-malarial efficacy of various compounds. The results indicate the potential of the XN-30 analyzer as a powerful tool for drug discovery and development in addition to its use as an important diagnostic tool.


Assuntos
Antimaláricos/farmacologia , Automação Laboratorial/instrumentação , Descoberta de Drogas/instrumentação , Hematologia/instrumentação , Antimaláricos/isolamento & purificação , Atovaquona/farmacologia , Automação Laboratorial/métodos , Cloroquina/farmacologia , Descoberta de Drogas/métodos , Hematologia/métodos , Humanos , Concentração Inibidora 50 , Malária Falciparum/tratamento farmacológico , Mefloquina/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Esquizontes/efeitos dos fármacos , Trofozoítos/efeitos dos fármacos
14.
J Pharm Pharmacol ; 71(2): 260-269, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30303245

RESUMO

OBJECTIVES: To assess the antiplasmodial activity of the ethanol extract of Xylopia sericea leaves, Annonaceae, often associated with antimalarial use and to perform a bioguided isolation of active compounds. METHODS: Dereplication of ethanol extract by the UPLC-DAD-ESI-MS/MS technique allowed the identification of the major constituents, isolation and identification of alkaloids. The antiplasmodial and cytotoxic activity of the extract, fractions and isolated compounds was evaluated against the chloroquine-resistant W2 strain Plasmodium falciparum and HepG2 cells, respectively. KEY FINDINGS: Ethanol extract showed high reduction of parasitemia as well as moderate cytotoxicity (86.5 ± 3.0% growth inhibition at 50 µg/ml and CC50 72.1 ± 5.1 µg/ml, respectively). A total of eight flavonoids were identified, and two aporphine alkaloids, anonaine and O-methylmoschatoline, were isolated. Anonaine disclosed significant antiplasmodial effect and moderate cytotoxicity (IC50 23.2 ± 2.7 µg/ml, CC50 38.3 ± 2.3 µg/ml, SI 1.6) while O-methylmoschatoline was not active against P. falciparum and showed a low cytotoxicity (33.5 ± 1.9% growth inhibition at 50 µg/ml, CC50 274.4 ± 0.5 µg/ml). CONCLUSIONS: Characterization of Xylopia sericea leaves ethanol extract by UPLC-DAD-ESI-MS/MS as well as its antiplasmodial activity and the occurrence of anonaine and O-methylmoschatoline in this Xylopia species are reported by the first time.


Assuntos
Alcaloides/farmacologia , Antimaláricos/farmacologia , Extratos Vegetais/farmacologia , Xylopia/química , Alcaloides/isolamento & purificação , Alcaloides/toxicidade , Antimaláricos/isolamento & purificação , Antimaláricos/toxicidade , Aporfinas/isolamento & purificação , Aporfinas/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Dioxóis/isolamento & purificação , Dioxóis/farmacologia , Etanol/química , Células Hep G2 , Humanos , Concentração Inibidora 50 , Extratos Vegetais/administração & dosagem , Extratos Vegetais/toxicidade , Folhas de Planta , Plasmodium falciparum/efeitos dos fármacos , Espectrometria de Massas em Tandem/métodos
15.
Chem Biol Drug Des ; 93(2): 147-153, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30216685

RESUMO

In the present study, a series of new esters of secochiliolide acid (SA), a diterpene isolated from Nardophyllum bryoides, were synthesized in good yield. All compounds were evaluated for their in vitro antiparasitic properties (on Plasmodium falciparum and Trypanosoma brucei brucei) and cytotoxicity (on WI38, normal mammalian cells). They displayed moderate antitrypanosomal activity with IC50 values between 2.55 and 18.14 µm, with selectivity indices >10, and low antiplasmodial effects with IC50  > 29 µm. The only exception was the n-hexyl ester of SA, which showed a strong and selective antiplasmodial activity (IC50  = 1.99 µm and selectivity index = 117.0). The in vivo antimalarial efficacy of this compound was then assessed according to the 4-day suppressive test of Peters in mice. An intraperitoneal treatment at 50 mg kg-1  day-1 induced a slight parasitaemia reduction by 56% which was statistically significant on day 4 post-infection and an increase in the survival time.


Assuntos
Antimaláricos/química , Antiprotozoários/química , Diterpenos/química , Ésteres/química , Propionatos/química , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Antiprotozoários/isolamento & purificação , Antiprotozoários/farmacologia , Asteraceae/química , Asteraceae/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Humanos , Extratos Vegetais/química , Plasmodium falciparum/efeitos dos fármacos , Propionatos/isolamento & purificação , Propionatos/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos
16.
Mini Rev Med Chem ; 19(15): 1204-1218, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30421673

RESUMO

As important marine biological resources, corals produce a large amount of active organic compounds in their secondary metabolic processes, including numerous brominated, chlorinated, and iodinated compounds. These compounds, with novel structures and unique activities, guide the discovery and research of important lead compounds and novel biological mechanisms. Through a large number of literature surveys, this paper summarized a total of 145 halogenated secondary metabolites which were roughly divided into four major classes of terpenes, prostaglandins, steroids and alkaloids, and they were mainly isolated from ten coral families, Ellisellidae, Gorgoniidae, Briareidae, Plexauridae, Anthothelidae, Alcyoniidae, Clavularidae, Tubiporidae, Nephtheidae and Dendrophyllidae to the best of our knowledge. In addition, their organism species, structure composition and biological activity were also discussed in the form of a chart in this essay.


Assuntos
Antozoários/química , Anti-Infecciosos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Antimaláricos/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Hidrocarbonetos Halogenados/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Antimaláricos/química , Antimaláricos/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Hidrocarbonetos Halogenados/química , Hidrocarbonetos Halogenados/isolamento & purificação , Conformação Molecular
17.
Nat Prod Res ; 33(6): 782-788, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29172699

RESUMO

The phytochemical investigation of an alkaloidal extract of Holarrhena pubescens roots led to the isolation and identification of a new pregnene-type alkaloid, mokluangin D (1), together with nine known steroidal alkaloids (2-10). The structure of the new metabolite was determined on the basis of spectroscopic analyses including 1D- and 2D-NMR spectroscopy and mass spectrometry. Compounds 3 and 4 showed potent antimalarial activity against Plasmodium falciparum K1 stain with IC50 values of 1.2 and 2.0 µM, respectively, and showed weak cytotoxic activity against the NCI-H187 cell line with IC50 values of 27.7 and 30.6 µM, respectively. The substituent groups at C-3 and the carbonyl group at C-18 are important for the activity against the P. falciparum K1 stain.


Assuntos
Alcaloides/farmacologia , Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Holarrhena/química , Pregnenos/farmacologia , Esteroides/farmacologia , Alcaloides/isolamento & purificação , Antimaláricos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Plasmodium falciparum/efeitos dos fármacos , Pregnenos/isolamento & purificação , Esteroides/isolamento & purificação , Tailândia
18.
Nat Prod Res ; 33(4): 568-572, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29086620

RESUMO

The present study explored the schizonticidal potential of traditionally used Magnolia champaca (L.) Baill. ex. Pierre flowers, identifying constituents of interest. The extraction of phytoconstituents was carried out by microwave-assisted technique, isolated via column chromatography, and characterised by various physicochemical, spectral (IR, 1H-NMR and Mass) and chromatographic (HPTLC) techniques. Both the isolated compounds (parthenolide and costunolide diepoxide) exhibited potent schizonticidal antimalarial activity during primary screening in rodent models, with maximum parasitaemia suppression (85.18% and 83.65%, respectively) at a dose of 20 mg/kg body weight when compared to the standard drugs chloroquine and artesunate. In silico techniques were employed to identify the probable biological target and mechanism of action of these isolated compounds. Molecular docking studies also predicted the binding orientations and multi-targeted action of these compounds, in particular costunolide diepoxide with maximum affinity towards SERCA and DHFR proteins. Additionally, favourable in silico ADMET parameters were envisaged through various computational programmes.


Assuntos
Antimaláricos/isolamento & purificação , Antiprotozoários/isolamento & purificação , Lactonas/isolamento & purificação , Magnolia/química , Sesquiterpenos/isolamento & purificação , Antimaláricos/farmacologia , Antiprotozoários/farmacologia , Cromatografia Líquida de Alta Pressão , Lactonas/química , Lactonas/farmacologia , Micro-Ondas , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Análise Espectral
19.
Artigo em Inglês | MEDLINE | ID: mdl-30448629

RESUMO

The aim of this study is to develop validated methods for the extraction and quantification of antimalarial triterpene esters from Keetia leucantha and from plasma samples. These compounds, showing in vitro and in vivo antiplasmodial activities, were optimally extracted from Keetia leucantha twigs using ultrasounds with dichloromethane and from plasma using protein precipitation with acetonitrile. We then developed and validated HPLC-UV quantification methods, which proved to be selective, accurate, linear, true and precise, both in plant and plasma samples for the eight triterpenic esters in mixture. Based on the total error concept as decision criteria, the validated dosage ranges of the triterpene esters mixture were set between 14.68 and 73.37 µg/mL in plants and 15.90 and 106.01 µg/mL in plasma injected solutions, corresponding to 7.95 and 53.01 µg/mL in plasma. These reliable methods were used to determine effectively triterpene esters content in collected samples, that seems highly variable in plant extracts, and will be helpful to further investigate pharmacokinetics parameters of these interesting bioactive compounds.


Assuntos
Antimaláricos , Extratos Vegetais/química , Rubiaceae/química , Triterpenos , Antimaláricos/análise , Antimaláricos/sangue , Antimaláricos/isolamento & purificação , Humanos , Modelos Lineares , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Triterpenos/análise , Triterpenos/sangue , Triterpenos/isolamento & purificação
20.
J Ethnopharmacol ; 228: 148-155, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30048730

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The Vha-Venda people living in rural areas of Limpopo Province of South Africa regularly use traditional plant-based medicines to treat malaria. In our earlier publication, twenty indigenous plant species used to treat malaria or its symptoms by Vha-Venda people were evaluated for antiplasmodial activity. The main objective of the current study was to assess the robustness of NMR-based metabolomics in discriminating classes of secondary compounds that are responsible for the observed antimalarial activity and the isolation of antiplasmodial compounds. MATERIALS AND METHODS: Twenty dichloromethane extracts were reconstituted in CDCl3, subjected to 1H NMR-based metabolomic analysis on a Varian 600 MHz spectrometer and the acquired 1H NMR spectra were then evaluated collectively using multivariate data analysis (MDA). Principal Component Analysis (PCA) and Orthogonal Projections to Latent Structures-Discriminant Analysis (OPLS-DA) were used to 'globally' discern antiplasmodial profiles. A contribution plot was then generated from the OPLS-DA scoring plot in an attempt to determine the classes of compounds that are responsible for the observed grouping. Further phytochemical analyses were conducted on the lipophilic extracts of Tabernaemontana elegans and Vangueria infausta subsp. infausta. These best candidates were fractionated, purified and their isolated compounds identified based on conventional chromatographic and spectroscopic techniques. RESULTS: The PCA did not separate the acquired profiles according to the detected antiplasmodial bioactivity. Application of a supervised OPLS-DA on the 1H NMR profiles resulted in a discrimination pattern that could be correlated to the observed antimalarial bioactivity. A contribution plot generated from the OPLS-DA scoring plot illustrated the classes of compounds responsible for the observed grouping. Prominent peaks were observed in the aromatic, sugar-based/N-containing and aliphatic spectral regions of the contribution plot. Two known indole alkaloids were isolated from T. elegans, and identified as tabernaemontanine (IC50 = 12.0 ±â€¯0.8 µM) and dregamine (IC50 = 62.0 ±â€¯2.4 µM). Friedelin (IC50 = 7.20 ±â€¯0.5 µM) and morindolide (IC50 = 107.1 ±â€¯0.6 µM) were isolated from V. infausta subsp. infausta. This is the first report of the rare iridoid lactone, morindolide's antimalarial activity. While these two compounds have been previously identified, this is the first account of their occurrence in the genus Vangueria. CONCLUSION: The study illustrated the potential of NMR-based metabolomics in discriminating classes of compounds that may be attributed to antiplasmodial activity. Additionally, the study demonstrated the potential of discovering novel antiplasmodial scaffolds from medicinal plants and the rationale for the bioprospecting antimalarial plant species used by Vha-Venda people.


Assuntos
Antimaláricos , Metabolômica , Compostos Fitoquímicos , Plantas Medicinais , Animais , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Linhagem Celular , Medicina Tradicional Africana , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Espectroscopia de Prótons por Ressonância Magnética , Ratos , África do Sul
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