In vitro activity of six antiviral drugs against equid alphaherpesvirus type 1 indicates ganciclovir as promising drug for in vivo studies

ABSTRACT In vitro studies have demonstrated that anidulafungin has greater potency than caspofungin against Candida glabrata. However, data from in vivo studies demonstrating that it has superior efficacy are lacking. The objective of this study was to compare the activities of anidulafungin and caspofungin against C. glabrata in a murine model of disseminated candidiasis. Two clinical C. glabrata isolates were used, including one with reduced caspofungin susceptibility. MICs were determined by broth microdilution in the presence and absence of sera. For the animal studies, mice were immunosuppressed with 5-fluorouracil one day prior to intravenous inoculation. Treatment with anidulafungin and caspofungin (0, 0.5, 1, 5, and 10 mg/kg of body weight per day) was begun 24 h later and was continued through day 7 postinoculation. The CFU were enumerated from kidney tissue. According to the standard microdilution methodology, anidulafungin had superior in vitro activity. However, this enhanced potency was attenuated by the addition of mouse and human sera. Caspofungin reduced the kidney fungal burden at lower doses compared to that achieved with anidulafungin in mice infected with the isolate with the lower MIC. Against the strain with the elevated caspofungin MIC, both anidulafungin and caspofungin were effective in reducing the kidney fungal burden at the higher doses studied. Despite the greater in vitro activity of anidulafungin in the absence of sera, both echinocandins were similarly effective in reducing the fungal burden in kidney tissue. The superior in vitro activity of anidulafungin did not confer enhanced in vivo efficacy against C. glabrata.

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Multidisciplinary Preclinical Investigations on Three Oxamniquine Analogues as Novel Treatment Options for Schistosomiasis

10.26434/chemrxiv.12102894 ◽

2020 ◽

Author(s):

Valentin Buchter ◽

Yih Ching Ong ◽

François Mouvet ◽

Abdallah Ladaycia ◽

Elise Lepeltier ◽

...

Keyword(s):

Treatment Options ◽

Vitro Activity ◽

In Vivo Studies ◽

In Vitro Activity ◽

Liver Model ◽

Novel Treatment ◽

Active Concentration ◽

Dynamics Simulations

<div>Schistosomiasis is a disease of poverty affecting millions of people. Praziquantel (PZQ), with its </div><div>strengths and weaknesses, is the only treatment available. We previously reported 3 lead </div><div>compounds derived from oxamniquine (OXA), an old antischistosomal drug: ferrocene‐containing </div><div>(Fc‐CH2‐OXA), ruthenocene‐containing (Rc‐CH2‐OXA) and benzene‐containing (Ph‐CH2‐OXA). </div><div>These derivatives showed excellent in vitro activity against both Schistosoma mansoni and S. </div><div>haematobium larvae and adult worms, and in vivo against S. mansoni. Encouraged by these </div><div>promising results, we followed a guided drug discovery process and report in this investigation on </div><div>metabolic stability studies, in vivo studies, computational simulations, and formulation studies. </div><div>Molecular dynamics simulations supported the in vitro results on the target protein. Though all </div><div>three compounds were poorly stable within an acidic environment, they were only slightly cleared </div><div>in the in vitro liver model. This is likely the reason as to why the promising in vitro activity did not </div><div>translate to in vivo activity. This limitation could not be saved by the formulation of lipid </div><div>nanocapsules as an intent to improve the in vivo activity. Further studies should focus on increasing </div><div>the compound’s bioavailability, in order to reach an active concentration in the parasite’s </div><div>microenvironment. </div>

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In vitro and in vivo efficacies of the azole SCH56592 against Cryptococcus neoformans.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.8.1910 ◽

1996 ◽

Vol 40 (8) ◽

pp. 1910-1913 ◽

Cited By ~ 98

Author(s):

J R Perfect ◽

G M Cox ◽

R K Dodge ◽

W A Schell

Keyword(s):

Central Nervous System ◽

Cryptococcus Neoformans ◽

Amphotericin B ◽

Central Nervous System Infection ◽

Rabbit Model ◽

Vitro Activity ◽

In Vitro Activity ◽

Drug Concentrations

Multiple isolates of Cryptococcus neoformans were tested to compare the in vitro activity of a new triazole, SCH56592, with those of amphotericin B, fluconazole, and itraconazole, MICs of each drug were determined, and minimum fungicidal concentrations of SCH56592 and amphotericin B were measured. MICs of SCH56592 were lower than those of amphotericin B and fluconazole but not those of itraconazole. Minimum fungicidal concentrations of SCH56592 were lower than those of amphotericin B. SCH56592 in the presence of human serum produces an in vitro fungicidal effect for Cryptococcus neoformans. The data indicate that SCH56592 might exert fungicidal as well as inhibitory properties in vivo. On the basis of these results, SCH56592 was evaluated with a rabbit model of experimental cryptococcal meningitis; SCH56592 treatment was compared with treatment with fluconazole. Despite no detectable drug concentrations in the cerebrospinal fluid, the activity of SCH56592 against C. neoformans infection was equivalent to that of fluconazole. SCH56592 has potent in vitro activity against C. neoformans and compares favorably to treatment with fluconazole for a central nervous system infection. SCH56592 should be studied for use in humans with cryptococcal infections.

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Multidisciplinary Preclinical Investigations on Three Oxamniquine Analogues as Novel Treatment Options for Schistosomiasis

10.26434/chemrxiv.12102894.v1 ◽

2020 ◽

Author(s):

Valentin Buchter ◽

Yih Ching Ong ◽

François Mouvet ◽

Abdallah Ladaycia ◽

Elise Lepeltier ◽

...

Keyword(s):

Treatment Options ◽

Vitro Activity ◽

In Vivo Studies ◽

In Vitro Activity ◽

Liver Model ◽

Novel Treatment ◽

Active Concentration ◽

Dynamics Simulations

<div>Schistosomiasis is a disease of poverty affecting millions of people. Praziquantel (PZQ), with its </div><div>strengths and weaknesses, is the only treatment available. We previously reported 3 lead </div><div>compounds derived from oxamniquine (OXA), an old antischistosomal drug: ferrocene‐containing </div><div>(Fc‐CH2‐OXA), ruthenocene‐containing (Rc‐CH2‐OXA) and benzene‐containing (Ph‐CH2‐OXA). </div><div>These derivatives showed excellent in vitro activity against both Schistosoma mansoni and S. </div><div>haematobium larvae and adult worms, and in vivo against S. mansoni. Encouraged by these </div><div>promising results, we followed a guided drug discovery process and report in this investigation on </div><div>metabolic stability studies, in vivo studies, computational simulations, and formulation studies. </div><div>Molecular dynamics simulations supported the in vitro results on the target protein. Though all </div><div>three compounds were poorly stable within an acidic environment, they were only slightly cleared </div><div>in the in vitro liver model. This is likely the reason as to why the promising in vitro activity did not </div><div>translate to in vivo activity. This limitation could not be saved by the formulation of lipid </div><div>nanocapsules as an intent to improve the in vivo activity. Further studies should focus on increasing </div><div>the compound’s bioavailability, in order to reach an active concentration in the parasite’s </div><div>microenvironment. </div>

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High in vitro activity of DIS-73285, a novel antimicrobial with a new mechanism of action, against MDR and XDR Neisseria gonorrhoeae

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa322 ◽

2020 ◽

Vol 75 (11) ◽

pp. 3244-3247

Author(s):

Susanne Jacobsson ◽

Clive Mason ◽

Nawaz Khan ◽

Paul Meo ◽

Magnus Unemo

Keyword(s):

Neisseria Gonorrhoeae ◽

Small Molecule ◽

Mechanism Of Action ◽

Vitro Activity ◽

In Vivo Studies ◽

In Vitro Activity ◽

Agar Dilution ◽

High Level

Abstract Background The rising incidence of antimicrobial resistance in Neisseria gonorrhoeae may result in untreatable gonorrhoea in certain circumstances and development of novel antimicrobials is urgently needed. Objectives To evaluate the in vitro activity of a novel small-molecule antimicrobial with a new mechanism of action, DIS-73285, against a large geographically, temporally and genetically diverse collection of clinical N. gonorrhoeae isolates and reference strains, including various types of high-level resistant, MDR and XDR gonococcal isolates (n = 262). Methods MICs (mg/L) of DIS-73285 were determined by agar dilution and by Etest for ceftriaxone, cefixime, azithromycin, ciprofloxacin, ampicillin, spectinomycin and tetracycline. Results DIS-73285 was substantially more potent than any of the currently or previously used therapeutic antimicrobials, with MICs ranging from ≤0.001 to 0.004 mg/L, and the MIC50, MIC90 and modal MIC all ≤0.001 mg/L (lowest MIC tested). No correlation with the MICs of DIS-73285 and the MICs of any of the currently or previously used antimicrobials was observed. Conclusions The novel chemotype, small-molecule antimicrobial DIS-73285, demonstrated high in vitro potency against all tested N. gonorrhoeae isolates. Further in vitro and in vivo studies, evaluating efficacy, resistance emergence, pharmacokinetic/pharmacodynamic parameters, toxicity and safety, should be conducted to evaluate DIS-73285 as a therapy specifically for urogenital and extra-genital gonorrhoea.

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ANTITUMOR EFFECT OF COLLOIDAL SILVER BISILICATE IN EXPERIMENTAL IN VITRO AND IN VIVO STUDIES

Problems in oncology ◽

10.37469/0507-3758-2019-65-5-760-765 ◽

2019 ◽

Vol 65 (5) ◽

pp. 760-765

Author(s):

Margarita Tyndyk ◽

Irina Popovich ◽

A. Malek ◽

R. Samsonov ◽

N. Germanov ◽

...

Keyword(s):

Antitumor Activity ◽

Tumor Growth ◽

Tumor Cells ◽

Human Tumor ◽

Significant Inhibition ◽

In Vivo Studies ◽

Ehrlich Carcinoma ◽

In Vivo Experiments

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.

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In Vitro and In Vivo Antibacterial Activities of DW-224a, a New Fluoronaphthyridone

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01407-05 ◽

2006 ◽

Vol 50 (6) ◽

pp. 2261-2264 ◽

Cited By ~ 36

Author(s):

Hee-Soo Park ◽

Hyun-Joo Kim ◽

Min-Jung Seol ◽

Dong-Rack Choi ◽

Eung-Chil Choi ◽

...

Keyword(s):

Antibacterial Activities ◽

The Other ◽

Vitro Activity ◽

Gram Negative Bacteria ◽

In Vitro Activity ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria

ABSTRACT DW-224a showed the most potent in vitro activity among the quinolone compounds tested against clinical isolates of gram-positive bacteria. Against gram-negative bacteria, DW-224a was slightly less active than the other fluoroquinolones. The in vivo activities of DW-224a against gram-positive bacteria were more potent than those of other quinolones.

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Evaluation of the in vitro activity and in vivo bioavailability of realgar nanoparticles prepared by cryo-grinding

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2006.05.002 ◽

2006 ◽

Vol 29 (1) ◽

pp. 35-44 ◽

Cited By ~ 75

Author(s):

Jin-Zhu Wu ◽

Paul C. Ho

Keyword(s):

Vitro Activity ◽

In Vitro Activity

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The Challenging Melanoma Landscape: From Early Drug Discovery to Clinical Approval

Cells ◽

10.3390/cells10113088 ◽

2021 ◽

Vol 10 (11) ◽

pp. 3088

Author(s):

Mariana Matias ◽

Jacinta O. Pinho ◽

Maria João Penetra ◽

Gonçalo Campos ◽

Catarina Pinto Reis ◽

...

Keyword(s):

Therapeutic Potential ◽

Drug Evaluation ◽

Three Dimensional ◽

Experimental Models ◽

In Vivo Studies ◽

Murine Models ◽

In Vivo Experiments ◽

Novel Therapeutic Strategies

Melanoma is recognized as the most dangerous type of skin cancer, with high mortality and resistance to currently used treatments. To overcome the limitations of the available therapeutic options, the discovery and development of new, more effective, and safer therapies is required. In this review, the different research steps involved in the process of antimelanoma drug evaluation and selection are explored, including information regarding in silico, in vitro, and in vivo experiments, as well as clinical trial phases. Details are given about the most used cell lines and assays to perform both two- and three-dimensional in vitro screening of drug candidates towards melanoma. For in vivo studies, murine models are, undoubtedly, the most widely used for assessing the therapeutic potential of new compounds and to study the underlying mechanisms of action. Here, the main melanoma murine models are described as well as other animal species. A section is dedicated to ongoing clinical studies, demonstrating the wide interest and successful efforts devoted to melanoma therapy, in particular at advanced stages of the disease, and a final section includes some considerations regarding approval for marketing by regulatory agencies. Overall, considerable commitment is being directed to the continuous development of optimized experimental models, important for the understanding of melanoma biology and for the evaluation and validation of novel therapeutic strategies.

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