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Novel microbial product having antifungal activity

A technology of drugs and compounds, applied in the direction of microorganisms, microorganisms, antifungal agents, etc., can solve the problems of obtaining new drug candidate compounds, obtaining promising new drug candidate compounds, etc., and achieve low reactivity and strong antifungal effect

Active Publication Date: 2016-09-21
SEED RES INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Surprisingly, however, no promising new drug candidates were obtained from the chemical library
In this situation, it is extremely difficult to obtain new drug candidates

Method used

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  • Novel microbial product having antifungal activity
  • Novel microbial product having antifungal activity
  • Novel microbial product having antifungal activity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Example 1: Isolation and analysis of Streptomyces sp.A84 strain

[0056] The isolated source was collected from the sea sand of Kakeroma Island, Kagoshima Prefecture. Strains were isolated from the collected samples, and the isolated microbial strains were evaluated and screened with antifungal activity as an index. As a result, promising strains were obtained, which were further examined in detail.

[0057] The strain was analyzed by phylogenetic analysis of 16S rRNA, and it was found that the producing bacteria were actinomycetes of the genus Streptomyces, and the related species were Streptomyces nodosus (98.8% homology) and Streptomyces glomeratus ) (99.0% homology). Since the nucleotide sequence homology with the closest relative Streptomyces glomeratus is 99.0%, this indicates the possibility of a new species. This strain was named as Streptomyces sp.A84 strain. The Streptomyces sp.A84 strain was deposited in Kisarazu City, Chiba Prefecture, at 2-5-8, 2-5-8,...

Embodiment 2

[0058] Example 2: Study of production medium for A84 strain

[0059] The production medium for the A84 strain was investigated.

[0060] As a result of the study of the medium, good productivity was shown in the following medium.

[0061] Medium composition:

[0062] Starch 4%

[0063] Case peptone 0.1%

[0064] NaH 2 PO 4 0.1%

[0065] Artificial seawater (MARINE ART SUPER FORMULA 1, manufactured by Tomita Pharmaceutical Co., Ltd.) 0.384%

[0066] pH 7.0

[0067] Cultivation conditions: A medium (100 ml) was filled into a 300-ml volume Erlenmeyer flask, and cultured at 28° C., 200 rpm for 2-4 days.

Embodiment 3

[0068] Example 3: Isolation, purification and analysis of active ingredients

[0069]The A84 strain was inoculated into a 300 ml volumetric Erlenmeyer flask supplemented with 100 ml of the medium having the composition described in Example 2, and cultured at 28° C., 200 rpm (rotary shaker) for 3 days. The broth was solvent extracted with an equal amount of ethyl acetate, and then the ethyl acetate was concentrated. The dried sample was dissolved in a small amount of methanol, and purified by column chromatography by HPLC using an ODS column (purity 95% or more, 100 μg / 1L).

[0070] LC / MS analysis, NMR analysis and optical rotation measurements of the active ingredient were carried out. The measurement conditions are as follows:

[0071] LC / MS:

[0072] Device: Model Agilent6540

[0073] Ion source: AJS-ESI, ESI, APC1

[0074] NMR:

[0075] Device: ECA-600 (manufactured by JEOL Ltd.)

[0076] Magnet: SCM 14.o1T

[0077] Bore diameter: 54mm

[0078] Probe: 3mm, 5mm, 1...

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Abstract

Provided are a compound having a novel scaffold that can serve as a seed compound for innovative drug development, use of the same as an antifungal, a method for production of the same, and the like. A compound represented by the formula or a pharmaceutically acceptable salt thereof, an antifungal containing the same, and the like.

Description

technical field [0001] The present invention relates to a compound having a novel parent nucleus, its use as an antifungal agent, its preparation method, and the like. Background technique [0002] In recent years, fungal infections such as the increase in the elderly population, the development of advanced medicine, and immunodeficiency in patients with advanced cancer have increased. These infections have serious consequences, often leading to death. Since existing antifungal drugs are few in number and their toxicity is high, there is a need for a parent nucleus of new antifungal agents that are different from existing drugs. In addition, due to the increase in the emergence of resistant bacteria due to the use of antifungal drugs, there is an urgent need for the development of new drugs. While Candida-based antifungals show low toxicity, their reactivity with serum poses problems due to their large molecular weight. Azole-based antifungals are difficult to administer ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D498/02A61K31/4375A61P31/10C12N1/20C12P1/04C12R1/465
CPCC12P17/14C07D498/04A61P31/10C12R2001/465C12N1/205A01N43/90
Inventor 石见盛太加藤幸松本佳巳直木秀夫
Owner SEED RES INST
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