<i>In Vitro</i>
            and
            <i>In Vivo</i>
            Efficacy of Novel Flavonoid Dimers against Cutaneous Leishmaniasis

Wong, Iris L. K.; Chan, Kin‐Fai; Chen, Yun-Fu; Lun, Zhao‐Rong; Chan, Tak Hang; Chow, Larry M.C.

doi:10.1128/aac.02425-13

Cited by 31 publications

(19 citation statements)

References 27 publications

(51 reference statements)

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“…To extend these findings, we have synthesized and evaluated the biological properties of a series of CAM homodimers. The potential benefits of this strategy, which has been proved useful in several other applications [ 13 , 23 – 26 ], include: (i) improvement of the biological activity of CAM, since the presence of dimers can occupy multiple functional sites of the target, (ii) enhancement of the binding affinity, because CAM dimers are capable of simultaneously binding two separated RNA sites, and (iii) better potency against resistant bacterial strains. Nevertheless, a number of drawbacks need to be considered when developing such antibacterials, like cell permeability problems and unexpected binding to additional targets, as has been reported in previous studies [ 11 , 23 – 26 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of Chloramphenicol Homodimers: Molecular Target, Antimicrobial Activity, and Toxicity against Human Cells

et al. 2015

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As fight against antibiotic resistance must be strengthened, improving old drugs that have fallen in reduced clinical use because of toxic side effects and/or frequently reported resistance, like chloramphenicol (CAM), is of special interest. Chloramphenicol (CAM), a prototypical wide-spectrum antibiotic has been shown to obstruct protein synthesis via binding to the bacterial ribosome. In this study we sought to identify features intensifying the bacteriostatic action of CAM. Accordingly, we synthesized a series of CAM-dimers with various linker lengths and functionalities and compared their efficiency in inhibiting peptide-bond formation in an Escherichia coli cell-free system. Several CAM-dimers exhibited higher activity, when compared to CAM. The most potent of them, compound 5, containing two CAM bases conjugated via a dicarboxyl aromatic linker of six successive carbon-bonds, was found to simultaneously bind both the ribosomal catalytic center and the exit-tunnel, thus revealing a second, kinetically cryptic binding site for CAM. Compared to CAM, compound 5 exhibited comparable antibacterial activity against MRSA or wild-type strains of Staphylococcus aureus, Enterococcus faecium and E. coli, but intriguingly superior activity against some CAM-resistant E. coli and Pseudomonas aeruginosa strains. Furthermore, it was almost twice as active in inhibiting the growth of T-leukemic cells, without affecting the viability of normal human lymphocytes. The observed effects were rationalized by footprinting tests, crosslinking analysis, and MD-simulations.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of Chloramphenicol Homodimers: Molecular Target, Antimicrobial Activity, and Toxicity against Human Cells

et al. 2015

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“…have been reported, and some of these compounds showed high efficacy in killing amastigotes and promastigotes of various Leishmania spp. both in vivo and in vitro (103)(104)(105)(106)(107).…”

Section: Treatment: Chemotherapymentioning

confidence: 99%

Visceral Leishmaniasis in China: an Endemic Disease under Control

Lun¹,

Wu²,

Chen³

et al. 2015

Clin Microbiol Rev

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SUMMARYVisceral leishmaniasis (VL) caused byLeishmaniaspp. is an important vector-borne and largely zoonotic disease. In China, three epidemiological types of VL have been described: anthroponotic VL (AVL), mountain-type zoonotic VL (MT-ZVL), and desert-type ZVL (DT-ZVL). These are transmitted by four different sand fly species:Phlebotomus chinensis,P. longiductus,P. wui, andP. alexandri.In 1951, a detailed survey of VL showed that it was rampant in the vast rural areas west, northwest, and north of the Yangtze River. Control programs were designed and implemented stringently by the government at all administrative levels, resulting in elimination of the disease from most areas of endemicity, except the western and northwestern regions. The control programs consisted of (i) diagnosis and chemotherapy of patients, (ii) identification, isolation, and disposal of infected dogs, and (iii) residual insecticide indoor spraying for vector control. The success of the control programs is attributable to massive and effective mobilization of the general public and health workers to the cause. Nationally, the annual incidence is now very low, i.e., only 0.03/100,000 according to the available 2011 official record. The overwhelming majority of cases are reported from sites of endemicity in the western and northwestern regions. Here, we describe in some depth and breadth the current status of epidemiology, diagnosis, treatment, and prevention of the disease, with particular reference to the control programs. Pertinent information has been assembled from scattered literature of the past decades in different languages that are not readily accessible to the scientific community. The information provided constitutes an integral part of our knowledge on leishmaniasis in the global context and will be of special value to those interested in control programs.

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“…Nonadherent cells were removed, and these cells were infected with stationary-phase promastigotes of L. donovani at a ratio of 6:1 (parasites/macrophages) and incubated at 37°C in 5% CO 2 for 0 to 18 h. At 18 h after the parasites entered macrophages, free parasites were eliminated, and infected macrophages were treated with increasing concentrations (0, 2.5, 5, and 10 g/ml) of synthesized Ag NPs and incubated at 37°C in 5% CO 2 for 24 h. After incubation for various times, infected macrophages treated with or without synthesized Ag NPs in chamber slides were fixed with ice-cold methanol, and slides were then submerged in 10% (vol/vol) Giemsa staining solution (Thomas Baker) for 45 min, briefly washed in water, and set to dry. The slides were viewed on an inverted bright-field microscope (IX73 inverted microscope; Olympus) (29). At least 100 macrophages per well from duplicate cultures were counted to calculate the percentage of infected macrophages using the following formula (30): % reduction ϭ number of amastigotes per 100 macrophages (treated samples)/number of amastigotes per 100 macrophages (infected control) ϫ 100.…”

Section: Synthesis Of Ag Nps and Tiomentioning

confidence: 99%

Green Synthesis of Silver and Titanium Dioxide Nanoparticles Using Euphorbia prostrata Extract Shows Shift from Apoptosis to G ₀ /G ₁ Arrest followed by Necrotic Cell Death in Leishmania donovani

Zahir¹,

Chauhan

Bagavan³

et al. 2015

Antimicrob Agents Chemother

153

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The aim of the present study was to synthesize silver (Ag) and titanium dioxide (TiO 2 ) nanoparticles (NPs) using green synthesis from aqueous leaf extract of Euphorbia prostrata as antileishmanial agents and to explore the underlying molecular mechanism of induced cell death. In vitro antileishmanial activity of synthesized NPs was tested against promastigotes of Leishmania donovani by alamarBlue and propidium iodide uptake assays. Antileishmanial activity of synthesized NPs on intracellular amastigotes was assessed by Giemsa staining. The leishmanicidal effect of synthesized Ag NPs was further confirmed by DNA fragmentation assay and by cell cycle progression and transmission electron microscopy (TEM) of the treated parasites. TEM analysis of the synthesized Ag NPs showed a spherical shape with an average size of 12.82 ؎ 2.50 nm, and in comparison to synthesized TiO 2 NPs, synthesized Ag NPs were found to be most active against Leishmania parasites after 24 h exposure, with 50% inhibitory concentrations (IC 50 ) of 14.94 g/ml and 3.89 g/ml in promastigotes and intracellular amastigotes, respectively. A significant increase in G 0 /G 1 phase of the cell cycle with a subsequent decrease in S (synthesis) and G 2 /M phases compared to controls was observed. The growth-inhibitory effect of synthesized Ag NPs was attributed to increased length of S phase. A decreased reactive oxygen species level was also observed, which could be responsible for the caspase-independent shift from apoptosis (G 0 /G 1 arrest) to massive necrosis. High-molecular-weight DNA fragmentation as a positive consequence of necrotic cell death was also visualized. We also report that the unique trypanothione/trypanothione reductase (TR) system of Leishmania cells was significantly inhibited by synthesized Ag NPs. The green-synthesized Ag NPs may provide promising leads for the development of costeffective and safer alternative treatment against visceral leishmaniasis.

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In Vitro and In Vivo Efficacy of Novel Flavonoid Dimers against Cutaneous Leishmaniasis

Cited by 31 publications

References 27 publications

Synthesis and Evaluation of Chloramphenicol Homodimers: Molecular Target, Antimicrobial Activity, and Toxicity against Human Cells

Synthesis and Evaluation of Chloramphenicol Homodimers: Molecular Target, Antimicrobial Activity, and Toxicity against Human Cells

Visceral Leishmaniasis in China: an Endemic Disease under Control

Green Synthesis of Silver and Titanium Dioxide Nanoparticles Using Euphorbia prostrata Extract Shows Shift from Apoptosis to G ₀ /G ₁ Arrest followed by Necrotic Cell Death in Leishmania donovani

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In Vitro and In Vivo Efficacy of Novel Flavonoid Dimers against Cutaneous Leishmaniasis

Cited by 31 publications

References 27 publications

Synthesis and Evaluation of Chloramphenicol Homodimers: Molecular Target, Antimicrobial Activity, and Toxicity against Human Cells

Synthesis and Evaluation of Chloramphenicol Homodimers: Molecular Target, Antimicrobial Activity, and Toxicity against Human Cells

Visceral Leishmaniasis in China: an Endemic Disease under Control

Green Synthesis of Silver and Titanium Dioxide Nanoparticles Using Euphorbia prostrata Extract Shows Shift from Apoptosis to G 0 /G 1 Arrest followed by Necrotic Cell Death in Leishmania donovani

Contact Info

Product

Resources

About

Green Synthesis of Silver and Titanium Dioxide Nanoparticles Using Euphorbia prostrata Extract Shows Shift from Apoptosis to G ₀ /G ₁ Arrest followed by Necrotic Cell Death in Leishmania donovani