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Compounds and methods for treating candidiasis and aspergillus infections

A technology for Aspergillus and candidiasis, which is applied in the directions of botanical equipment and methods, applications, and drug combinations, and can solve problems such as liver damage

Inactive Publication Date: 2016-03-16
CELLCEUTIX CORP +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, some antifungal drugs may cause liver damage

Method used

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  • Compounds and methods for treating candidiasis and aspergillus infections
  • Compounds and methods for treating candidiasis and aspergillus infections
  • Compounds and methods for treating candidiasis and aspergillus infections

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[1160] Example 1: Screening for anti-Candida activity

[1161] More than 800 compounds were screened against clinical isolates of C. albicans GDH2346 at a single concentration of 10 μM (see below figure 1 triangle in ) and an additional 400 compounds were screened at 11 concentrations for IC 50 (see below figure 1 green square in ). Pass OD at 24 and 48 hours 600 and fluorescence to determine activity.

[1162] 106 compounds showed greater than 90% inhibition, giving a 12% hit rate. These compounds are all bactericidal. 109 compounds showed IC 50 IC of 50 <10 μg / mL.

Embodiment 2

[1163] Embodiment 2: antibacterial silk activity

[1164] Candida albicans (GDH2346) was grown in 10% FCS for 3 days to produce hyphae. Treat mycelia with compound 100 (8 μg / mL) for 0 min (see Figure 2A ), 15 minutes (see Figure 2B ), 30 minutes (see Figure 2C ) or 60 minutes (see Figure 2D ). Cultures were stained with Funga photovitamin (InVitrogen) and observed under a fluorescent microscope (100X magnification).

[1165] At low concentrations, compound 100 rapidly caused the death of mycelial cultures.

Embodiment 3

[1166] Example 3: Permeabilization

[1167] (A) C. albicans GDH2346 was treated with compound 100 at the indicated concentrations (μg / mL) for 30 minutes, then stained with PI and quantified by flow cytometry. Ethanol treatment was used to create 100% absorption.

[1168] (B) Cells were treated with 32 μg / mL of Compound 100 for the indicated times.

[1169] Compound 100 was assessed for its ability to permeabilize membranes in order to determine whether the compound acts on membranes like many host defense proteins or whether the compound acts intracellularly like histamine. Dose-dependent membrane permeabilization of Candida at concentrations of 8 to 32 μg / mL Compound 100, as shown by cell accumulation by PI, was evident within 30 minutes (see Figure 3A ). Following 5 min treatment with 32 μg / mL Compound 100, influx was rapid with >75% of cells permeabilized (see Figure 3B ).

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PUM

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Abstract

The present invention provides methods for killing or inhibiting the growth of Candida or Aspergillus species and preventing or treating oral or disseminated candidiasis or Aspergillus infection in mammals A surface amphiphilic antimicrobial oligomer, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof for mammals infected with disease or Aspergillus spp. The method of use comprises contacting a Candida or Aspergillus species with a mammal in need thereof or administering to a mammal in need thereof an effective amount of such an antibacterial oligomer, a pharmaceutically acceptable salt thereof, or a pharmaceutical combination thereof thing.

Description

technical field [0001] The present invention relates in part to compounds, or pharmaceutically acceptable salts thereof, for use in the treatment of mammals suffering from candidiasis and / or Aspergillus infection, such as oral candidiasis and / or disseminated candidiasis and Pharmaceutical compositions and methods comprising them. Background technique [0002] Candidiasis encompasses fungal infections caused by various species of Candida, in particular mainly Candida albicans, which is a yeast-like fungus. Candida is commonly found in the mouth, vagina and intestines of healthy individuals; normal bacteria in these areas keep the amount of Candida under control. Infection by the Candida fungus generally usually relies on a weakened immune state of the individual to attack tissues that are usually resistant to infection and gain access to the circulatory system. Candida infections that develop in immunocompromised individuals can affect the systemic body (eg, disseminated or...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A01N25/00
CPCC07C279/04C07C279/06C07C211/29A61K31/381A61K31/404A61K31/4192A61K31/4436A61K31/496A61K31/505C07C211/27C07C211/28C07C217/20C07C279/08C07C279/12C07D209/86C07D239/26C07D239/28C07D239/38C07D249/06C07D277/28C07D307/52C07D307/91C07D333/20C07D333/76C07D409/14A61P17/00A61K31/506A61P31/10C07C237/08A01N25/00A61K9/0053A61K9/06
Inventor 理查德·W·斯科特凯蒂·弗里曼唐海忠吉勒·戴蒙德
Owner CELLCEUTIX CORP
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