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1.
In this study, we are reporting antileishmanial activity of a marine sponge Haliclona exigua, belonging to phylum Porifera. The crude methanol extract and its three fractions were tested both in vitro and in vivo.
The crude extract exerted almost complete inhibition of promastigotes at 50 μg/ml and 76.4 ± 6.5% inhibition of intracellular
amastigotes at 100 μg/ml concentration with IC50 values of 18.6 μg/ml and 47.2 μg/ml, respectively. When administered to Leishmania donovani infected hamsters at a dose of 500 mg/kg × 5, p.o., it resulted in 72.2 ± 10.4% inhibition of intracellular amastigotes.
At a lower dose (250 mg/kg), it exhibited 43.9 ± 5.1% inhibition. Among the fractions, highest antileishmanial activity both
in vitro (>90%) and in vivo (60.9 ± 18.3%) was observed in n-butanol (soluble) fraction with IC50 values of 8.2 μg/ml and 31.2 μg/ml against promastigotes and intracellular amastigotes, respectively. Hexane fraction also
showed comparatively good activity against both the stages of parasites in vitro but was moderately active in leishmania-infected
hamsters. Chloroform fraction resulted in 45 ± 10.2% inhibition in vivo at a dose of 500 mg/kg × 5, p.o., whereas it was inactive
in vitro. n-Butanol (insoluble) fraction was inactive both in vitro and in vivo. Araguspongin C, an alkaloid isolated from n-butanol (soluble) fraction exhibited moderate inhibition of promastigotes and intracellular amastigotes at 100 μg/ml but
showed weak antileishmanial action in vivo. Our findings indicate that this marine sponge has the potential to provide new
lead toward development of an effective antileishmanial agent and, hence, calls for more exhaustive studies for exploiting
the vast world of marine resources to combat the scourge of several parasitic diseases. 相似文献
2.
The chemotherapeutic interventions against visceral leishmaniasis (VL) are limited and facing serious concerns of toxicity,
high cost, and emerging drug resistance. There is a greater interest in new drug developments from traditionally used medicinal
plants which offers unprecedented diversity in structures and bioactivity. With this rationale, ethanolic extract of Tinospora sinensis Linn and its four fractions were tested in vitro against promastigotes and intracellular amastigotes and in vivo in Leishmania donovani infected hamsters. Ethanolic extract exhibited an appreciable activity against promastigotes (IC50 37.6 ± 6.2 μg/ml) and intracellular amastigotes (IC50 29.8 ± 3.4 μg/ml). In hamsters, it resulted in 76.2 ± 9.2% inhibition at 500 mg/kg/day × 5 oral dose level. Among fractions,
n-butanol imparted highest in vitro and in vivo activities. Ethanolic extract and butanol fraction also enhances reactive oxygen
species (ROS) and nitric oxide (NO) release. The results indicate that T. sinensis may provide new lead molecules for the development of alternative drugs against VL. 相似文献
3.
Pujals G Suñé-Negre JM Pérez P García E Portus M Tico JR Miñarro M Carrió J 《Parasitology research》2008,102(6):1243-1247
The aim of the present study was to evaluate the in vitro activity and cytotoxicity of meglumine antimoniate microspheres
produced by spray drying on Leishmania infantum and the effect of the excipients used in them. The parasite strain shows sensitivity to the meglumine antimoniate microspheres
prepared. All the antimony IC50 values from encapsulated meglumine antimoniate (3.80 ± 0.34 to 9.53 ± 0.70 μg SbV/ml for promastigotes assay) are considerably
lower compared to the mean value of IC50 in Glucantime solution (112 ± 12.74 μg SbV/ml). Interesting IC50 values for the excipient chitosan (112.64 ± 0.53 mg/ml for promastigotes and 100.81 ± 26.45 mg/ml for amastigotes) were obtained
(without cytotoxic activity), whereas the rest of the excipients did not show any activity. This new delivery system could
offer a new pharmacological tool for the treatment of leishmaniosis that reduces the doses required, lowering toxic side effects
because of meglumine antimoniate. 相似文献
4.
Shuaibu MN Wuyep PA Yanagi T Hirayama K Tanaka T Kouno I 《Parasitology research》2008,102(6):1119-1127
In vitro antiplasmodial activity of methanolic extracts of 16 medicinal plants was evaluated by fluorometric assay using PicoGreen.
The IC50s, as determined by parasite DNA concentration, ranged from <11 to >200 and <13 to >200 μg/ml for Plasmodium falciparum 3D7 and K1, respectively; and the most active extracts were those from Anogeissus leiocarpus and Terminalia avicennoides (<11–≥14 μg/ml). Aqueous, butanolic, ethyl acetate, and methanolic fractions of these two extracts revealed butanolic fraction
to have a relatively better activity (IC50, 10–12 μg/ml). Activity-guided chromatographic separation of the butanolic fraction on Sephadex LH-20 followed by nuclear
magnetic resonance and correlation high-performance liquid chromatography revealed the presence of known hydrolysable tannins
and some related compounds—castalagin, ellagic acid, flavogallonic acid, punicalagin, terchebulin, and two other fractions.
The IC50s of all these compounds ranged between 8–21 μg/ml (8–40 μM) against both the strains. Toxicity assay with mouse fibroblasts
showed all the extracts and isolated compounds to have IC50 ≥ 1500 μg/ml, except for Momordica balsamina with <1500 μg/l. All the extracts and isolated compounds did not affect the integrity of human erythrocyte membrane at the
observed IC50s. However, adverse effects manifest in a concentration-dependent fashion (from IC50 ≥ 500 μg/ml). 相似文献
5.
In the present investigation, we have evaluated the antileishmanial and antitrypanosomal activity of methanolic crude extracts
obtained from eight species of cnidarians and of a modified steroid isolated from the octocoral Carijoa riisei. The antileishmanial activity of cnidarians crude extracts showed 50% inhibitory concentration (IC50) values in the concentration range between 2.8 and 93.3 μg/mL. Trypomastigotes of Trypanosoma cruzi were less susceptible to the crude extracts, with IC50 values in the concentration range between 40.9 and 117.9 μg/mL. The steroid (18-acetoxipregna-1,4,20-trien-3-one) displayed
a strong antileishmanial activity, with an IC50 value of 5.5 μg/mL against promastigotes and 16.88 μg/mL against intracellular amastigotes. The steroid also displayed mammalian
cytotoxicity (IC50 of 10.6 μg/mL), but no hemolytic activity was observed at the highest concentration of 12.5 μg/mL. The antileishmanial effect
of the steroid in macrophages suggested other mechanism than macrophage activation, as no upregulation of nitric oxide was
observed. The antitrypanosomal activity of the steroid resulted in an IC50 value of 50.5 μg/mL. These results indicate the potential of cnidarian natural compounds as antileishmanial drug candidates. 相似文献
6.
Santoro GF das Graças Cardoso M Guimarães LG Salgado AP Menna-Barreto RF Soares MJ 《Parasitology research》2007,100(4):783-790
In the present work, we have investigated the effect of essential oils obtained from Origanum vulgare L. (oregano) and Thymus vulgaris L. (thyme) on growth and ultrastructure of diverse evolutive forms of Trypanosoma cruzi. Culture epimastigotes and bloodstream trypomastigotes were incubated for 24 h with different concentrations of oregano or
thyme essential oils and with thymol (the main constituent of thyme), and the inhibitory concentration (IC)50 was determined by cell counting. Crude extract of oregano essential oil inhibited epimastigote growth (IC50/24 h = 175 μg/ml) and also induced trypomastigote lysis (IC50/24 h = 115 μg/ml). Thyme essential oil presented IC50/24 h values of 77 μg/ml for epimastigotes and 38 μg/ml for trypomastigotes, while treatment with thymol resulted in an IC50/24 h of 62 μg/ml for epimastigotes and 53 μg/ml for trypomastigotes. Scanning electron microscopy of treated cells showed
few morphological alterations at the plasma membrane. Observation by transmission electron microscopy showed cytoplasmic swelling
with occasional morphological alterations in plasma and flagellar membrane. Our data indicate that oregano and thyme essential
oils are effective against T. cruzi, with higher activity of thyme, and that thymol may be the main component responsible for the trypanocidal activity. 相似文献
7.
Marta Regina Santin Adriana Oliveira dos Santos Celso Vataru Nakamura Benedito Prado Dias Filho Izabel Cristina Piloto Ferreira Tania Ueda-Nakamura 《Parasitology research》2009,105(6):1489-1496
Leishmaniasis causes considerable mortality throughout the world, affecting more than 12 million people. Cymbopogon citratus (DC) Stapf, Family Poaceae, is a widely used herb in tropical countries and is also known as a source of ethnomedicines.
In this study, the inhibitory effect and the morphological and ultrastructural alterations on Leishmania amazonensis by the essential oil (EO) of C. citratus and its main constituent, citral, were evaluated. The results showed that the antiproliferative activity of EO on promastigotes
and axenic amastigotes, and intracellular amastigote forms of L. amazonensis was significantly better than citral, and indicated a dose-dependent effect. Neither compound showed a cytotoxic effect on
macrophage strain J774G8. The promastigote forms of L. amazonensis underwent remarkable morphological and ultrastructural alterations compared with untreated cultures. These alterations were
visible by light, scanning, and transmission electron microscopy of promastigotes treated with EO and citral at concentrations
corresponding to the IC50 (1.7 and 8.0 μg/ml) and IC90 (3.2 and 25 μg/ml), respectively, after 72 h of incubation. This study revealed that citral-rich essential oil from C. citratus has promising antileishmanial properties, and is a good candidate for further research to develop a new anti-protozoan drug. 相似文献
8.
Olounladé PA Azando EV Hounzangbé-Adoté MS Ha TB Leroy E Moulis C Fabre N Magnaval JF Hoste H Valentin A 《Parasitology research》2012,110(4):1427-1433
The need for new anthelmintic with no chemical residues is becoming urgent. In a program aiming at the evaluation of plant
as sources of new active molecules, the anthelmintic activities of the essential oils (EOs) obtained from either Zanthoxylum zanthoxyloides seeds or Newbouldia laevis leaves were evaluated against Strongyloides ratti by analyzing the results of two in vitro bioassays. These two plants and their tested parts were retained after an ethnopharmacology
survey that confirmed their use by small-scale farmers for treatment of small ruminants affected by digestive helminths. The
plants were harvested in Benin, and their EO were obtained by hydrodistillation. The EO yield of extraction was 0.65% (w/w)
of for Z. zanthoxyloides seeds and 0.05% (w/w) for N. laevis. The chemical compositions of the two EOs were analyzed by gas chromatography coupled with mass spectrometry. The major constituents
of the EO from Z. zanthoxyloides consisted of the following compounds: γ-terpinene (18 %), undecane (15 %), valencene (8.3 %), decanal (8.3 %), and 3-carene
(6.7 %). In contrast, the major constituents of the EO from N. laevis leaves consisted of the following compounds: β-caryophyllene (36 %) and eugenol (5.8 %). An egg-hatching inhibition (EHI)
assay was developed and a larval migration inhibition assay was used on S. ratti to examine the effects of the EOs and to evidence their inhibitory concentrations (IC50 and IC90) values on this nematode. Furthermore, the toxicity of the two EOs on Vero cell line was evaluated. When tested on S. ratti egg hatching, the two EOs resulted in similar IC50 values (19.5 and 18.2 μg/ml for Z. zanthoxyloides and N. laevis, respectively), which were about sevenfold higher than that of the control (thiabendazole, IC50 = 2.5 μg/ml). Larval migration was inhibited at similar concentrations for: Z. zanthoxyloides (IC50 = 46 μg/ml), N. laevis (IC50 = 51 μg/ml), and the control [levamisole (IC50 = 36 μg/ml)]. No cytotoxicity was found on Vero cells because both EOs had IC50 values higher than 50 μg/ml. Therefore, we have concluded that the EOs from two plants, used in folk medicine, may contain
compounds with anthelmintic activity and could be used as improved traditional medicines or, at least, as food additives in
a combined treatment for the control of helminth infections. 相似文献
9.
Ruiyan Zhang Liming Shang Hongtao Jin Cuiping Ma Yongkui Wu Quan Liu Zhiping Xia Feng Wei Xing-Quan Zhu Hongwei Gao 《Parasitology research》2010,107(2):475-479
Control of Leishmania infection relies primarily on chemotherapy, and the current drug available for treating leishmaniasis is limited. Nitazoxanide
(NTZ) is a broad spectrum antiparasitic agent with activity against protozoa, nematodes, cestodes, and trematodes. In the
present study, the in vitro antileishmanial efficacy of NTZ was evaluated by incubation of Leishmania donovani promastigotes with NTZ, indicating that NTZ can affect the ultrastructure of parasite promastigote and efficiently inhibit
the parasite growth. Moreover, 200 μg/ml NTZ inhibited >90% of promastigotes growth, showing similar activity of the reference
drug amphotericin B (P > 0.05). Therapeutic efficacy of NTZ against L. donovani-infected BALB/c mice demonstrated that oral NTZ produced a significant reduction of parasite burden in spleen and liver from
L. donovani-infected mice, compared with the untreated mice (P < 0.05). These results indicated NTZ may be a novel therapeutic drug for leishmaniasis. 相似文献
10.
Passero LF Tomokane TY Corbett CE Laurenti MD Toyama MH 《Parasitology research》2007,101(5):1365-1371
In this study, we compared the anti-leishmanial activity of three crotalic venoms (Crotalus durissus terrificus–Cdt, Crotalus durissus cascavella–Cdca, and Crotalus durissus collilineatus–Cdcol). Different concentrations of each venom incubated with Leishmania (Leishmania) amazonensis promastigotes were used. Cdt venom exhibited a higher anti-leishmanial activity (Inhibitory concentration-IC50-value of 4.70 ± 1.72 μg/ml) in comparison
with that of Cdca venom (IC50 value of 9.41 ± 1.21 μg/ml), while Cdcol venom increased parasite numbers in 50% at a concentration of 44.30 ± 2.18 μg/ml. In addition, this venom showed a low anti-leishmanial
activity in higher concentrations (IC50 value of 281.00 ± 9.50 μg/ml). The main fractions of Cdca venom were isolated and assayed under similar conditions used for assessing crude venom. The most active fractions were gyroxin
and crotamine that had IC50 values of 3.80 ± 0.52 μg/ml and 19.95 ± 4.21 μg/ml, respectively. Convulxin also inhibited parasite
growth rate, although this effect was not dose-dependent. Crotoxin was the least effective fraction with an IC50 value of
99.80 ± 2.21 μg/ml. None of the protein fractions presented cytotoxic effects against J774 cells in culture. In vivo assays
using BALB/c mice revealed that crotoxin and crotamine were the main toxic fractions. In conclusion, C. durissus cascavella venom has three main fractions with anti-leishmanial activity. These results open new possibilities to find proteins that
might be used as possible agents against cutaneous leishmaniasis. 相似文献
11.
Sawangjaroen N Phongpaichit S Subhadhirasakul S Visutthi M Srisuwan N Thammapalerd N 《Parasitology research》2006,98(6):588-592
The anti-amoebic activities of chloroform, methanol and water extracts from 12 Thai medicinal plants (39 extracts) commonly used by AIDS patients in southern Thailand were screened, at a concentration of 1,000 μg/ml, against Entamoeba histolytica strain HTH-56:MUTM and strain HM1:IMSS growing in vitro. The extracts were incubated with 2×105
E. histolytica trophozoites/ml of medium at 37°C under anaerobic conditions for 24 h. The cultures were examined with an inverted microscope and scored (1–4) according to the appearance and numbers of the trophozoites. The extracts that caused inhibition were selected and retested using the same conditions but with concentrations that ranged from 31.25 to 1,000 μg/ml using E. histolytica strain HM1:IMSS, and the IC50 values for each extract were calculated. The chloroform extracts from Alpinia galanga (IC50 55.2 μg/ml), Barleria lupulina (IC50 78.5 μg/ml), Boesenbergia pandurata (IC50 45.8 μg/ml), Piper betle (IC50 91.1 μg/ml) and Piper chaba (IC50 71.4 μg/ml) and the methanol extract from B. pandurata (IC50 57.6 μg/ml) were all classified as “active”, i.e. with an IC50 of less than 100 μg/ml, whereas those from Murraya paniculata (IC50 116.5 μg/ml) and Zingiber zerumbet (IC50 196.9 μg/ml) were classified as being “moderately active”. The IC50 of a standard drug, metronidazole, was 1.1 μg/ml. 相似文献
12.
Passero LF Castro AA Tomokane TY Kato MJ Paulinetti TF Corbett CE Laurenti MD 《Parasitology research》2007,101(3):677-680
The crude methanolic extract from leaves of Jacaranda puberula showed activity against Leishmania (Leishmania) amazonensis. The extract presented active against promastigote forms with an inhibitory concentration 50% (IC50) value of 88.0 μg/ml, but only moderated activity against amastigote forms; however in higher concentrations the extract
showed cytotoxic effects. The bio-guided chromatographic fractionation the crude methanolic extract against amastigotes yielded
a fraction with an IC50 value of 14.0 μg/ml (without cytotoxic activity) in relation to the crude extract (IC50 value, 359.0 μg/ml). These data indicate that J. puberula leaves contain active compounds, which should be further investigated for the development of new potential drugs against
cutaneous leishmaniasis. 相似文献
13.
Moon HI 《Parasitology research》2007,100(5):1147-1149
Samples of Carpesium genus used as traditional remedies for the treatment of parasite infections were collected, and methanol extracts were obtained
by sonication. The ethylacetate-, n-butanol- and H2O-soluble fractions exhibited weak antiplasmodial activity (IC50 > 100 μg/ml; IC50, 50% inhibitory concentration). However, the chloroform fraction exhibited more impressive antiplasmodial activity (IC50 = 8.2 μg/ml). The antiplasmodial activity of the chloroform fractions was evaluated in vitro against the chloroquine-resistant
D10 strain of Plasmodium falciparum. Bioactivity-guided isolation of the chloroform fractions of the whole plants of Carpesium rosulatum has led to the isolation of a sesquiterpene lactone, ineupatorolides A, displaying high antiplasmodial activity (IC50 = 0.007 μg/ml). This is the first report of the isolation of ineupatorolides A from this species and of its remarkable antiplasmodial
activity. 相似文献
14.
In order to assess the potential of the stem bark of Kigelia africana (Lam.) Benth as source of new anti-malarial leads, n-hexane and ethyl acetate (EtOAc) extracts and four compounds isolated
from the stem bark were screened in vitro against the chloroquine-resistant W-2 and two field isolates of Plasmodium falciparum using lactate dehydrogenase assay. The products were also tested for their cytotoxicity on LLC/MK2 monkey kidney cells. The
EtOAc extract exhibited a significant antiplasmodial activity (IC50 = 11.15 μg/mL on W-2; 3.91 and 4.74 μg/mL on field CAM10 and SHF4 isolates, respectively), whereas the n-hexane fraction
showed a weak activity (IC50 = 73.78 μg/mL on W-2 and 21.85 μg/mL on SHF4). Three out of the four compounds showed good activity against all the three
different parasite strains (IC50 < 5 μM). Specicoside exhibited the highest activity on W-2 (IC50 = 1.54 μM) followed by 2β, 3β, 19α-trihydroxy-urs-12-en-28-oic acid (IC50 = 1.60 μM) and atranorin (IC50 = 4.41 μM), while p-hydroxycinnamic acid was the least active (IC50 = 53.84 μM). The EtOAc extract and its isolated compounds (specicoside and p-hydroxycinnamic acid) were non-cytotoxic (CC50 > 30 μg/mL), whereas the n-hexane extract and two of its products, atranorin and 2β, 3β, 19α-trihydroxy-urs-12-en-28-oic
acid showed cytotoxicity at high concentrations, with the last one being the most toxic (CC50 = 9.37 μg/mL). These findings justify the use of K. africana stem bark as antimalaria by traditional healers of Western Cameroon, and could constitute a good basis for further studies
towards development of new leads or natural drugs for malaria. 相似文献
15.
Shokri A Sharifi I Khamesipour A Nakhaee N Fasihi Harandi M Nosratabadi J Hakimi Parizi M Barati M 《Parasitology research》2012,110(3):1113-1117
Pentavalent antimonials are the standard treatment for cutaneous leishmaniasis (CL) with low efficacy and resistance is emerging.
CL is increased significantly in respect to incidence rate and expanding to new foci. In the present study, the effect of
verapamil on in vitro susceptibility of promastigote and amastigote stages of Leishmania tropica to meglumine antimoniate (MA, Glucantime) was evaluated using colorimetric assay (MTT) and in a macrophage model, respectively.
Verapamil, as a calcium channel blocker, affects drug uptake by preventing of drug efflux from the cells. In promastigote
form, several concentrations of MA with or without verapamil showed significant decrease (P < 0.05) in optical density. The overall mean IC50 value with combination of MA plus verapamil (IC50 = 116.03 μg/ml) was significantly less than MA (IC50 = 225.14 μg/ml) alone
(P < 0.05) for promastigote stage. Similarly, the amastigote stage was more susceptible to treatment with MA plus verapamil
to that of MA alone (P < 0.05). Analysis of overall effect of different concentrations of MA alone, compared with combination of MA plus verapamil
by mean infection rate of amastigotes in each macrophage showed a significant difference (P < 0.05).These findings indicated some degree of synergistic effects between MA and verapamil on in vitro susceptibility of
L. tropica to MA. Further works are required to evaluate this synergistic effect on animal model or volunteer human subjects. 相似文献
16.
K.-H. Hung J.-J. Yan Y.-C. Lu H.-M. Chen J.-J. Wu 《European journal of clinical microbiology & infectious diseases》2011,30(10):1181-1184
The Clinical Laboratory Standards Institute recommends that if both cefoxitin and oxacillin are tested against Staphylococcus aureus and either result is measured as resistant, the organism should be reported as oxacillin resistant. This indicates that discrepancies
may be present between oxacillin and cefoxitin sensitivities in S. aureus. In this study, we aimed to investigate the discrepancy between oxacillin and cefoxitin susceptibility in S. aureus clinical isolates. Of 10,980 S. aureus isolates recovered from 2005 to 2010, 27 (0.3%) isolates with discordant results between oxacillin and cefoxitin were collected.
Fourteen (oxacillin diameters 10–12 mm) of the 27 strains were susceptible (MICs = 0.5–2 μg/ml) and 13 (6–13 mm) were resistant
(4–>256 μg/ml) to oxacillin. The cefoxitin MICs of 14 oxacillin-susceptible and 13 oxacillin-resistant strains ranged between
4 and 8 and 8 to 32 μg/ml, respectively. Discrepancies were present between oxacillin and cefoxitin in S. aureus, and these strains should be further tested for oxacillin MICs and for the mecA gene or β-lactamase activity. 相似文献
17.
The effect of two protein kinase inhibitors, staurosporine and H-7, on the growth, morphology and infectivity of Leishmania major and Leishmania amazonensis promastigotes was examined. Incubation with H-7 (600 μM) for up to one hour had no effect on parasite growth, morphology
or infectivity. Staurosporine, however, was cytotoxic for promastigotes and incubation for 1, 5 or 15 minutes with 10 μM inhibitor
killed 19, 34 and 59 %, respectively, of the parasites. Longer incubations, up to one hour, at this concentration did not
increase parasite killing. However, treatment with 25 μM staurosporine for one hour was highly toxic, only 4 % of the promastigotes
surviving after 72 h. Lower concentrations of staurosporine, 0.25 and 2.5 μM, had only minor effects on parasite growth. Incubation
of either L. major or L. amazonensis with staurosporine (10 μM for 10 minutes) caused marked morphological changes in the size and appearance of the flagellar
pocket, and/or cytoplasm of the viable parasites. Treated parasites were still capable of infecting mouse peritoneal macrophages
and causing disease in BALB/c mice, though the treated parasites were less virulent than control promastigotes. These results
indicate that staurosporine, while inhibiting promastigote growth, does not prevent differentiation to amastigotes and amastigote
replication.
Received: 26 June 1996 / Accepted: 20 August 1996 相似文献
18.
Antiparasitic activity of biochanin A,an isolated isoflavone from fruits of <Emphasis Type="Italic">Cassia fistula</Emphasis> (Leguminosae) 总被引:1,自引:0,他引:1
Sartorelli P Carvalho CS Reimão JQ Ferreira MJ Tempone AG 《Parasitology research》2009,104(2):311-314
The fractionation through bioguided antileishmanial activity of the dichloromethane extract of Cassia fistula fruits (Leguminosae) led to the isolation of the active isoflavone biochanin A, identified by spectroscopic methods. This
compound showed 50% effective concentration (EC50) value of 18.96 μg/mL against promastigotes of Leishmania (L.) chagasi. The cytotoxicity of this substance against peritoneal macrophages resulted in an EC50 value of 42.58 μg/mL. Additionally, biochanin A presented an anti-Trypanosoma-cruzi activity, resulting in an EC50 value of 18.32 μg/mL and a 2.4-fold more effectiveness than benznidazole. These results contribute with novel antiprotozoal
compounds for future drug design studies. 相似文献
19.
Enedina Jiménez-Cardoso Leticia Eligio-García Adrián Cortés-Campos Andrés Flores-Luna Pedro Valencia-Mayoral Irma Lozada-Chávez 《Parasitology research》2009,105(1):25-33
Giardia intestinalis can develop resistance to albendazole, although the molecular mechanism is not understood. The aim of this study was to investigate
the differences and permanent mutation in the β-giardin gene of G. intestinalis strains: sensitive, resistant, or recovered-resistance to albendazole. The β-giardin gene was amplified by nested polymerase
chain reaction. The IC50 values varied from 0.29 to 0.38 μg/mL for strains sensitive to albendazole. For resistant strains, the IC50 range was 1.31–2.12 μg/mL. Recovered-sensitivity albendazole strains’ IC50 values were 0.33–0.49 μg/mL, and for strains with recovered-resistance, the IC50 was 1.42–2.74 μg/mL. β-giardin amplicon (720 bp) was sequenced and analysis sequence revealed several amino acid mutations
from resistant and recovered-sensitive strains of G. intestinalis. Most of the mutations were located in the ROD domain of β-giardin with a change from the sequence “TIARERA” in sensitive
strains instead “IDRPRE” in resistant strains. A comparative sequence analysis in resistant, recovered-sensitive, and resistant-recovered
strains revealed permanent mutation. This is the first report of combinatorial serine–proline–arginine repeats in the ROD
domain of β-giardin, whereas such repeats have been reported previously in the HEAD domain of SF-assemblin proteins. This
is the first time that the resistance to albendazole correlates with genetics but it is not necessarily caused by mutations
in the β-giardin gene of G. intestinalis. 相似文献
20.
Moreno D Plano D Baquedano Y Jiménez-Ruiz A Palop JA Sanmartín C 《Parasitology research》2011,108(1):233-239
In the present study, a family of 15 imidothio- and imidoselenocarbamates (1–15) analogs have been synthesized and screened
for their in vitro antileishmanial potential against Leishmania infantum promastigotes. The six most active ones (2, 4, 7, 13, 14, and 15) were also tested in an axenic amastigote model. In order
to establish their selectivity indexes (SI) the cytotoxic effect of each compound was also assayed against Jurkat and THP-1
cell lines. Compounds 2 and 4, both with a pyridine moiety, showed a moderate antileishmanial activity with an IC50 value of 4.68 ± 0.46 and 3.03 ± 0.24 μM, respectively, in the amastigote model. The activity was compared with that of standard
drugs, edelfosine (IC50 = 0.82 ± 0.13 μM) and miltefosine (IC50 = 2.84 ± 0.10 μM). Related to selectivity, the SI of both compounds are similar to those of the standard drugs when compared
against the THP-1 cell line. Moreover, compound 4 was able to reduce the number of amastigote-infected THP-1 cells to 40%
of that observed in untreated controls after a 96-h period of treatment. These derivatives thus represent two new leads for
further studies aimed at establishing their mechanism of action. 相似文献