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1.
Luiz Francisco Rocha e Silva Emerson Silva Lima Marne Carvalho de Vasconcellos Ellen Suzany Pereira Aranha David Siqueira Costa Elba Vieira Mustafa Sabrina Kelly Reis de Morais Maria das Gra?as Costa Alecrim Sergio Massayoshi Nunomura Lena Struwe Valter Ferreira de Andrade-Neto Adrian Martin Pohlit 《Memórias do Instituto Oswaldo Cruz》2013,108(4):501-507
Tachia sp. are used as antimalarials in the Amazon Region and
in vivo antimalarial activity of a Tachia sp. has been
previously reported. Tachia grandiflora Maguire and Weaver is
an Amazonian antimalarial plant and herein its cytotoxicity and antimalarial
activity were investigated. Spectral analysis of the tetraoxygenated xanthone
decussatin and the iridoid aglyone amplexine isolated, respectively, from the
chloroform fractions of root methanol and leaf ethanol extracts was performed.
In vitro inhibition of the growth of Plasmodium falciparum
Welch was evaluated using optical microscopy on blood smears. Crude extracts of
leaves and roots were inactive in vitro. However, chloroform fractions of the
root and leaf extracts [half-maximal inhibitory concentration (IC50) = 10.5 and
35.8 µg/mL, respectively] and amplexine (IC50= 7.1 µg/mL) were active in vitro.
Extracts and fractions were not toxic to type MRC-5 human fibroblasts (IC50>
50 µg/mL). Water extracts of the roots of T. grandiflora
administered by mouth were the most active extracts in the Peters 4-day
suppression test in Plasmodium berghei-infected mice. At 500
mg/kg/day, these extracts exhibited 45-59% inhibition five to seven days after
infection. T. grandiflora infusions, fractions and isolated
substance have potential as antimalarials. 相似文献
2.
Anna CC Aguiar Ananda C Cunha Isabela Penna Ceravolo Regina A Correia Gon?alves Arildo JB Oliveira Antoniana Ursine Krettli 《Memórias do Instituto Oswaldo Cruz》2015,110(7):906-913
Several species of Aspidosperma plants are used to treat diseases in
the tropics, including Aspidosperma ramiflorum, which acts against
leishmaniasis, an activity that is experimentally confirmed. The species, known as
guatambu-yellow, yellow peroba,
coffee-peroba andmatiambu, grows in the Atlantic
Forest of Brazil in the South to the Southeast regions. Through a guided
biofractionation of A. ramiflorum extracts, the plant activity
against Plasmodium falciparum was evaluated in vitro for toxicity
towards human hepatoma G2 cells, normal monkey kidney cells and nonimmortalised human
monocytes isolated from peripheral blood. Six of the seven extracts tested were
active at low doses (half-maximal drug inhibitory concentration < 3.8 µg/mL); the
aqueous extract was inactive. Overall, the plant extracts and the purified compounds
displayed low toxicity in vitro. A nonsoluble extract fraction and one purified
alkaloid isositsirikine (compound 5) displayed high selectivity indexes (SI) (= 56
and 113, respectively), whereas compounds 2 and 3 were toxic (SI < 10). The
structure, activity and low toxicity of isositsirikine in vitro are described here
for the first time in A. ramiflorum, but only the neutral and
precipitate plant fractions were tested for activity, which caused up to 53%
parasitaemia inhibition of Plasmodium berghei in mice with
blood-induced malaria. This plant species is likely to be useful in the further
development of an antimalarial drug, but its pharmacological evaluation is still
required. 相似文献
3.
Akihiro Sugawara Toshiaki Tanaka Tomoyasu Hirose Aki Ishiyama Masato Iwatsuki Yoko Takahashi Kazuhiko Otoguro Satoshi Ōmura Toshiaki Sunazuka 《Bioorganic & medicinal chemistry letters》2013,23(8):2302-2305
Borrelidin, a structurally unique 18-membered macrolide, was found to express antimalarial activity against drug-resistant Plasmodium falciparum malaria parasites, with IC50 value of 0.93 ng/mL. However, it also displays strong cytotoxicity against human diploid embryonic MRC-5 cells. To investigate the issue of the cytotoxicity of borrelidin, borrelidin-based analogues were synthesized and their anti-Plasmodium properties were evaluated. In this communication, we report that a novel borrelidin analogue, bearing the CH2SPh moiety via a triazole linkage, was found to retain a potent antimalarial activity, against drug-sensitive and drug-resistant parasite strains, but possess only weak cytotoxicity against human cells. 相似文献
4.
Andrade-Neto VF Brandão MG Nogueira F Rosário VE Krettli AU 《International journal for parasitology》2008,38(13):1505-1511
Most medicinal plants used against malaria in endemic areas aim to treat the acute symptoms of the disease such as high temperature fevers with periodicity and chills. In some endemic areas of the Brazilian Amazon region one medicinal plant seems to be an exception: Ampelozyziphus amazonicus, locally named “Indian beer” or “Saracura-mira”, used to prevent the disease when taken daily as a cold suspension of powdered dried roots. In previous work we found no activity of the plant extracts against malaria blood parasites in experimentally infected animals (mice and chickens) or in cultures of Plasmodium falciparum. However, in infections induced by sporozoites, chickens treated with plant extracts were partially protected against Plasmodium gallinaceum and showed reduced numbers of exoerythrocytic forms in the brain. We now present stronger evidence that the ethanolic extract of “Indian beer” roots hampers in vitro and in vivo development of Plasmodium berghei sporozoites, a rodent malaria parasite. Some mice treated with high doses of the plant extract did not become infected after sporozoite inoculation, whereas others had a delayed prepatent period and lower parasitemia. Our data validates the use of “Indian beer” as a remedy for malaria prophylaxis in the Amazon, where the plant exists and the disease represents an important problem which is difficult to control. Studies aiming to identify the active compounds responsible for the herein described causal prophylactic activity are needed and may lead to a new antimalarial prophylactic. 相似文献
5.
Bianca Pérez Cátia Teixeira Ana S. Gomes Inês S. Albuquerque Jiri Gut Philip J. Rosenthal Miguel Prudêncio Paula Gomes 《Bioorganic & medicinal chemistry letters》2013,23(3):610-613
Novel 9-aminoacridine derivatives were synthesized by linking the heteroaromatic core to different cinnamic acids through an aminobutyl chain. The test compounds demonstrated mid-nanomolar in vitro activity against erythrocytic stages of the chloroquine-resistant W2 strain of the human malaria parasite Plasmodium falciparum. Two of the most active derivatives also showed in vitro activity against liver-stage Plasmodium berghei, with activity greater than that of the reference liver-stage antimalarial primaquine. The compounds were not toxic to human hepatoma cells at concentrations up to 5 μM. Hence, 9-(N-cinnamoylbutyl)aminoacridines are a new class of leads for prevention and treatment of malaria. 相似文献
6.
Sabine Specht Daniel Fernández Ruiz Bettina Dubben Susanne Deininger Achim Hoerauf 《Microbes and infection / Institut Pasteur》2010,12(8-9):635-642
Filarial nematodes achieve long survival in their hosts due to their capacity to modulate immune responses. Therefore, immunomodulation by filarial nematodes may alter responses to concomitant infections such as malaria. Cerebral malaria (CM), a severe complication of Plasmodium falciparum infections, is triggered as a consequence of the immune response developed against malaria parasites. The question arises whether prior infection with helminth parasites is beneficial against CM. In the present work a murine model for subsequent has been used to assess this hypothesis. C57BL/6 mice were infected with the rodent filarial parasite Litomosoides sigmodontis and the murine model parasite for CM, Plasmodium berghei ANKA. Previously filaria-infected C57BL/6 mice showed significantly reduced CM rates. CD8+ T cell recruitment to the brain, a hallmark for CM development, was reduced in protected mice. Furthermore, in contrast to P. berghei single-infected animals, filaria-infected mice had significantly higher levels of circulating IL-10. The requirement for IL-10 in CM protection was demonstrated by the lack of protection in IL-10 KO mice. This suggests that the anti-inflammatory IL-10 elicited by filarial nematodes is able to suppress the overwhelming inflammatory reaction otherwise triggered against malaria parasites in C57BL/6 mice, preventing full progress to CM. 相似文献
7.
Mamoru Niikura Shigeru Kamiya Kiyoshi Kita 《International journal for parasitology》2010,40(1):101-108
Cerebral malaria is an infrequent but serious complication of Plasmodium falciparum infection in humans. Co-infection with different Plasmodium species is common in endemic areas and the existence of benign malaria parasites, such as Plasmodium vivax, during P. falciparum infection has been considered to reduce the risk of developing pathogenesis. However, it is still unknown how disease severity is reduced in the host during co-infection. In the present study, we investigated the influence of co-infection with non-lethal malaria parasites, Plasmodium berghei (Pb) XAT strain, on the outcome of Pb ANKA strain infection which causes experimental cerebral malaria (ECM) in mice. The co-infection with non-lethal Pb XAT suppressed ECM caused by Pb ANKA infection and prolonged survival of mice. The production of TNF-α and IFN-γ, which had been shown to be involved in development of ECM, was suppressed in co-infected mice early in infection. The suppression of ECM by co-infection with Pb XAT was abrogated in IL-10-deficient mice. IL-10 plays a crucial role in the suppression of ECM by co-infection with non-lethal malaria parasites, probably due to its suppressive effect on the induction of TNF-α and IFN-γ. Co-infection with Pb XAT and Pb ANKA is a useful model for understanding how ECM is suppressed. 相似文献
8.
The protozoan pathogens responsible for malaria are from the Plasmodium genus, with Plasmodium falciparum and Plasmodium vivax accounting for almost all clinical infections. With recent estimates of mortality exceeding 800,000 annually, malaria continues to take a terrible toll on lives and the early promises of medicine to eradicate the disease have yet to approach realization, in part due to the spread of drug resistant parasites. Recent reports of artemisinin-resistance have prompted renewed efforts to identify novel therapeutic options, and one such pathway being considered for antimalarial exploit is the parasite's programmed cell death (PCD) pathway. In this mini-review, we will discuss the roles of the plasmodium mitochondria in cell death and as a target of antimalarial compounds, taking into account recent data suggesting that PCD pathways involving the mitochondria may be attractive antimalarial targets. 相似文献
9.
10.
Reik Löser Jiri Gut Philip J. Rosenthal Maxim Frizler Michael Gütschow Katherine T. Andrews 《Bioorganic & medicinal chemistry letters》2010,20(1):252-255
Azadipeptide nitriles—novel cysteine protease inhibitors—display structure-dependent antimalarial activity against both chloroquine-sensitive and chloroquine-resistant lines of cultured Plasmodium falciparum malaria parasites. Inhibition of parasite’s hemoglobin-degrading cysteine proteases was also investigated, revealing the azadipeptide nitriles as potent inhibitors of falcipain-2 and -3. A correlation between the cysteine protease-inhibiting activity and the antimalarial potential of the compounds was observed. These first generation azadipeptide nitriles represent a promising new class of compounds for antimalarial drug development. 相似文献
11.
Background
Nyctanthes arbor-tristis (Harshringar, Night Jasmine) has been traditionally used in Ayurveda, Unani and other systems of medicine in India. The juice of its leaves has been used by various tribal populations of India in treatment of fevers resembling malaria.Aim of the study
This work reports the antiplasmodial activity guided fractionation of Harshringar leaves extract.Methodology
Crude ethanolic Harshringar leaves extract and its RPHPLC purified fractions were studied for antiplasmodial potency against 3D7 (CQ sensitive) and Dd2 (CQ resistant) strains of P.falciparum and subsequently subjected to bioassay guided fractionation using reverse phase chromatography to pursue the isolation of active fractions.Principal Findings
Harshringar crude leaves extract and some of its RPHPLC purified fractions exhibited promising antiplasmodial potency against 3D7 and Dd2 strains of P.falciparum.Conclusions
The present study has provided scientific validity to the traditional use of leaves extract of Harshringar against malaria leading to the conclusion that this plant holds promise with respect to antimalarial phytotherapy. This is the first scientific report of antiplasmodial activity of RPHPLC fractions of Harshringar leaves extract against P.falciparum strains. 相似文献12.
《Biochimica et Biophysica Acta - Proteins and Proteomics》2020,1868(3):140362
BackgroundThe malaria parasite Plasmodium falciparum expresses four related papain-family cysteine proteases known as falcipains. These proteases play critical roles in the parasite life cycle, and as such are potential targets for new modes of antimalarial chemotherapy, as discussed in this review.Scope of reviewThis review summarizes available knowledge describing falcipain cysteine proteases of malaria parasites.Major conclusionsBased on available data the falcipains can be broken into two sub-families, the falcipain-1 and the falcipain-2/3 sub-families. Falcipain-1 has been difficult to study; it appears to play its most important roles in nonerythrocytic parasites, but not the erythrocytic stage responsible for human disease. Falcipain-2 and falcipain-3 have similar biochemical features, and are expressed sequentially during the erythrocytic cycle. Inhibition of either of these enzymes blocks hemoglobin hydrolysis and completion of the parasite developmental cycle. Knockout of falcipain-2 blocks hemoglobin hydrolysis, but parasites recover, presumably due to subsequent expression of falcipain-3. Knockout of falcipain-3 has not been possible, suggesting that the protease is essential for erythrocytic parasites. Determination of structures of falcipains and extensive chemistry efforts have facilitated identification of numerous small molecule falcipain inhibitors as potential new antimalarial agents. Other malaria parasites express close homologs of falcipain-1 and falcipain-2/3 proteases, suggesting that agents that target the falcipains will also be active against other human malaria parasites.General Significance. Falcipain-2 and falcipain-3 play vital roles during the erythrocytic stage of infection with P. falciparum and thus are promising targets for new agents to treat malaria. 相似文献
13.
Nugroho AE Sugai M Hirasawa Y Hosoya T Awang K Hadi AH Ekasari W Widyawaruyanti A Morita H 《Bioorganic & medicinal chemistry letters》2011,21(11):3417-3419
Two new indole alkaloids, bisnicalaterine D (1), consisting of an eburnane and a corynanthe type of skeletons, and nicalaterine A (2) were isolated from the bark of Hunteria zeylanica. Their structures were elucidated by various spectroscopic data such as NMR and CD spectra. A series of bisnicalaterines and nicalaterine A showed potent antiplasmodial activity against Plasmodium falciparum 3D7. 相似文献
14.
James Chadwick Michael Jones Amy E. Mercer Paul A. Stocks Stephen A. Ward B. Kevin Park Paul M. O’Neill 《Bioorganic & medicinal chemistry》2010,18(7):2586-2597
A series of artemisinin–spermidine conjugates designed to utilise the upregulated polyamine transporter found in cancer cells have been prepared. These conjugates were evaluated against human promyelocytic leukaemia HL-60 cells and chloroquine-sensitive 3D7 Plasmodium falciparum and several show promising anticancer and antimalarial activity. Although some limitations in this vector-based approach are apparent, a number of high potency Boc-protected analogues were identified with activity against malaria parasites as low as 0.21 nM. 相似文献
15.
Charlotte V. Hobbs Jillian Neal Solomon Conteh Liam Donnelly Jingyang Chen Kennan Marsh Lynn Lambert Sachy Orr-Gonzalez Jessica Hinderer Sara Healy William Borkowsky Scott R. Penzak Sumana Chakravarty Stephen L. Hoffman Patrick E. Duffy 《PloS one》2014,9(7)
We have previously shown that the HIV protease inhibitor lopinavir-ritonavir (LPV-RTV) and the antibiotic trimethoprim sulfamethoxazole (TMP-SMX) inhibit Plasmodium liver stages in rodent malarias and in vitro in P. falciparum. Since clinically relevant levels are better achieved in the non-human-primate model, and since Plasmodium knowlesi is an accepted animal model for the study of liver stages of malaria as a surrogate for P. falciparum infection, we investigated the antimalarial activity of these drugs on Plasmodium knowlesi liver stages in rhesus macaques. We demonstrate that TMP-SMX and TMP-SMX+LPV-RTV (in combination), but not LPV-RTV alone, inhibit liver stage parasite development. Because drugs that inhibit the clinically silent liver stages target parasites when they are present in lower numbers, these results may have implications for eradication efforts. 相似文献
16.
《Redox report : communications in free radical research》2013,18(5):280-283
AbstractNew drugs against malaria are urgently and continuously needed. Plasmodium parasites are exposed to higher fluxes of reactive oxygen species and need high activities of intracellular antioxidant systems. A most important antioxidative system consists of (di)thiols which are recycled by disulfide reductases (DR), namely both glutathione reductases (GR) of the malarial parasite Plasmodium falciparum and man, and the thioredoxin reductase (TrxR) of P. falciparum. The aim of our interdisciplinary research is to substantiate DR inhibitors as antimalarial agents. Such compounds are active per se but, in addition, they can reverse thiol-based resistance against other drugs in parasites. Reversal of drug resistance by DR inhibitors is currently investigated for the commonly used antimalarial drug chloroquine (CQ). Our recent strategy is based on the synthesis of inhibitors of the glutathione reductases from parasite and host erythrocyte. With the expectation of a synergistic or additive effect, double-headed prodrugs were designed to be directed against two different and essential functions of the malarial parasite P. falciparum, namely glutathione regeneration and heme detoxification. The prodrugs were prepared by linking bioreversibly a GR inhibitor to a 4-aminoquinoline moiety which is known to concentrate in the acidic food vacuole of parasites. Drug-enzyme interaction was correlated with antiparasitic action in vitro on strains resistant towards CQ and in vivo in Plasmodium berghei-infected mice as well as absence of cytotoxicity towards human cells. Because TrxR of P. falciparum was recently shown to be responsible for the residual glutathione disulfide-reducing capacity observed after GR inhibition in P. falciparum, future development of antimalarial drug-candidates that act by perturbing the redox equilibrium of parasites is based on the design of new double-drugs based on TrxR inhibitors as potential antimalarial drug candidates. 相似文献
17.
Larissa Rodrigues Gomes Paulo Renato Rivas Totino Maria Carmen Arroyo Sanchez Elsa Paula da Silva Kaingona Daniel Cristiana Santos de Macedo Filomeno Fortes José Rodrigues Coura Silvia Maria Di Santi Guilherme Loureiro Werneck Martha Cecilia Suárez-Mutis Maria de Fátima Ferreira-da-Cruz Cláudio Tadeu Daniel-Ribeiro 《Memórias do Instituto Oswaldo Cruz》2013,108(6):796-800
Anti-glycosylphosphatidylinositol (GPI) antibodies (Abs) may reflect and mediate,
at least partially, anti-disease immunity in malaria by neutralising the toxic
effect of parasitic GPI. Thus, we assessed the anti-GPI Ab response in
asymptomatic individuals living in an area of the Brazilian Amazon that has a
high level of malaria transmission. For comparative purposes, we also
investigated the Ab response to a crude extract prepared from Plasmodium
falciparum, the merozoite surface protein (MSP)3 antigen of
P. falciparum and the MSP 1 antigen of Plasmodium
vivax (PvMSP1-19) in these individuals and in Angolan
patients with acute malaria. Our data suggest that the Ab response against
P. falciparum GPI is not associated with P.
falciparum asymptomatic infection in individuals who have been
chronically exposed to malaria in the Brazilian Amazon. However, this Ab
response could be related to ongoing parasitaemia (as was previously shown) in
the Angolan patients. In addition, our data show that PvMSP1-19may be
a good marker antigen to reflect previous exposure to
Plasmodium in areas that have a high transmission rate of
P. vivax. 相似文献
18.
Sung-Eun Lee Mi-Ran Kim Jeong-Han Kim Gary R. Takeoka Tae-Wan Kim Byeoung-Soo Park 《Phytomedicine》2008,15(6-7):533-535
Antimalarial activity of anthothecol, a limonoid of Khaya anthotheca (Meliaceae) against Plasmodium falciparum was tested using a [3H]-hypoxanthine and 48 h culture assay in vitro. Anthotechol showed potent antimalarial activity against malaria parasites with IC50 values of 1.4 and 0.17 μM using two different assays. Also, gedunin had antimalarial activity with IC50 values of 3.1 and 0.14 μM. However, the citrus limonoids, limonin and obacunone did not show any antimalarial activity. The antimalarial activities were compared with the three currently used antimalarial medicines quinine, chloroquinine and artemisinin. 相似文献
19.
《Saudi Journal of Biological Sciences》2022,29(4):2475-2482
Ethnopharmacology relevanceMorinda lucida is an ethnopharmacologically important plant that has traditionally been used to treat malaria in the Southwest of Nigeria. The aim of this study is to look into the antiplasmodial properties of different solvent extracts of Morinda lucida bark and leaves.Materials and methodsThe antiplasmodial model, (or curative assay), was tested against Plasmodium berghei NK65, a chloroquine-sensitive Plasmodium berghei strain. In experimental mice, parasitaemia, percentage inhibition, weight changes, and packed cell volume were measured and compared to chloroquine (10 mg kg?1). Standard phytochemical procedures were used to evaluate the extracts' chemo-profile.Results and DiscussionPhytochemical analysis of the extracts revealed the presence of tannins, alkaloids, steroids, saponins, phenols, and alkaloids, among other metabolites. The highest quantities of total phenolic, total tannins, and total flavonoid content were found in 50% ethanolic extracts. There was significant decrease in the body weight of the mice after inoculation, however, after administration of crude extracts, an increase in weight was observed. A negative variation (-3.00 g) was observed in group without treatment. The ethanolic crude extracts (200 and 400 mg/kg) significantly increased the packed cell volume compared to other extracts. CQ treated experimental mice showed 100% inhibition with activity greater than extracts treated groups. The lowest inhibitory effect was observed in 200 mg/kg ethanolic bark extract treated group with activity of 72.16%. The antiplasmodial activities exhibited by these extracts could be linked to the chemical constituents investigated.ConclusionThe findings of this study suggest the use of M. lucida leaves and bark as a medicinal agent for malaria treatment and as a potential source of effective antimalarial templates. Further research is needed to determine the safety and toxicological profile of these extracts in vivo. 相似文献
20.
Maria Rebelo Claudia Sousa Howard M. Shapiro Maria M. Mota Martin P. Grobusch Thomas H?nscheid 《PloS one》2013,8(4)
Resistance of Plasmodium falciparum to almost all antimalarial drugs, including the first-line treatment with artemisinins, has been described, representing an obvious threat to malaria control. In vitro antimalarial sensitivity testing is crucial to detect and monitor drug resistance. Current assays have been successfully used to detect drug effects on parasites. However, they have some limitations, such as the use of radioactive or expensive reagents or long incubation times. Here we describe a novel assay to detect antimalarial drug effects, based on flow cytometric detection of hemozoin (Hz), which is rapid and does not require any additional reagents. Hz is an optimal parasite maturation indicator since its amount increases as the parasite matures. Due to its physical property of birefringence, Hz depolarizes light, hence it can be detected using optical methods such as flow cytometry. A common flow cytometer was adapted to detect light depolarization caused by Hz. Synchronized in vitro cultures of P. falciparum were incubated for 48 hours with several antimalarial drugs. Analysis of depolarizing events, corresponding to parasitized red blood cells containing Hz, allowed the detection of parasite maturation. Moreover, chloroquine resistance and the inhibitory effect of all antimalarial drugs tested, except for pyrimethamine, could be determined as early as 18 to 24 hours of incubation. At 24 hours incubation, 50% inhibitory concentrations (IC50) were comparable to previously reported values. These results indicate that the reagent-free, real-time Hz detection assay could become a novel assay for the detection of drug effects on Plasmodium falciparum. 相似文献