CN107286091B - Application of amino Sclerotiorin derivative in preparation of anti-tuberculosis drugs - Google Patents

Application of amino Sclerotiorin derivative in preparation of anti-tuberculosis drugs Download PDF

Info

Publication number
CN107286091B
CN107286091B CN201610218004.6A CN201610218004A CN107286091B CN 107286091 B CN107286091 B CN 107286091B CN 201610218004 A CN201610218004 A CN 201610218004A CN 107286091 B CN107286091 B CN 107286091B
Authority
CN
China
Prior art keywords
tuberculosis
preparation
sclerotiorin
application
amino
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201610218004.6A
Other languages
Chinese (zh)
Other versions
CN107286091A (en
Inventor
邵长伦
王长云
魏美燕
牟晓凤
王翠芳
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ocean University of China
Original Assignee
Ocean University of China
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ocean University of China filed Critical Ocean University of China
Priority to CN201610218004.6A priority Critical patent/CN107286091B/en
Publication of CN107286091A publication Critical patent/CN107286091A/en
Application granted granted Critical
Publication of CN107286091B publication Critical patent/CN107286091B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
    • C07D217/18—Aralkyl radicals
    • C07D217/20—Aralkyl radicals with oxygen atoms directly attached to the aromatic ring of said aralkyl radical, e.g. papaverine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
    • C07D217/18—Aralkyl radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

An application of an amino Sclerotiorin derivative in preparation of an anti-tuberculosis drug is that the compounds 1, 2, 3 and 4 in the formula I have a strong inhibiting effect on mycobacterium tuberculosis tyrosine phosphatase (mTPB), and the IC50 of the compounds is 200 mu M, 126.42 mu M, 114.55 mu M and 200 mu M respectively. The invention provides an antituberculosis drug, which is characterized in that the compound shown in the formula I or the pharmaceutically acceptable salt thereof is applied to the preparation of the antituberculosis drug.

Description

Application of amino Sclerotiorin derivative in preparation of anti-tuberculosis drugs
Technical Field
The invention relates to application of an amino Sclerotiorin derivative in preparation of an anti-tuberculosis drug, in particular to application of an amino Sclerotiorin derivative with extremely strong inhibitory activity to mycobacterium tuberculosis tyrosine phosphatase (mTPB) in preparation of an anti-tuberculosis drug.
Background
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mycobacterium tuberculosis) that seriously endangers human health. 2011 world health organization reports that about 140 million people die from Tuberculosis (TB) and 870 ten thousand newly discovered patients. A key problem concerning tuberculosis is that it is susceptible to drug resistance, and drug-resistant tuberculosis (DR-TB) is a worldwide disease for which the public urgently needs to discover and develop new methods for treating tuberculosis. The research on the mechanism of tuberculosis and the development of new antitubercular drugs aiming at specific targets are directly related to the health of human beings and the development of society, mycobacterium tuberculosis tyrosine phosphatase (mPTPB) is an important virulence factor secreted by mycobacterium tuberculosis and used for promoting host infection by manipulating a signal transduction pathway, and the virulence factor is secreted by the mycobacterium tuberculosis and enters macrophages to organize the start of a host immune system and regulate the survival of bacteria in the host, so that the mycobacterium tuberculosis tyrosine phosphatase becomes a new target for screening tuberculosis drugs and is considered as a promising target for treating tuberculosis. But also research on finding new inhibitors of mycobacterium tuberculosis tyrosine phosphatase (mPTPB) is increasing. The unique living environment (high pressure, high salt, oxygen deficiency, light resistance and the like) of the marine microorganism promotes the marine microorganism to metabolize to generate a large amount of compounds with novel structures and good activity, and provides an important source for developing a novel mycobacterium tuberculosis tyrosine phosphatase (mTPB) inhibitor or a potential tuberculosis treatment drug.
(Makafe G G, Cao Y, Tan Y, et al. Antimicrob. Agents. Ch., 2016, Doi:10.1128/AAC.00152-16. Huang X, Huang H, Li H, et al. Org. Lett., 2013, 15(4):721723. Wang C, Wang J, Huang Y, et al. Molecules, 2013, 18(2): 17281740.)。
Disclosure of Invention
The invention aims to provide application of an amino Sclerotiorin derivative derived from marine fungi in preparation of anti-tuberculosis drugs, which can meet the above requirements of the prior art. Strain preservation information: the name of the depository: china general microbiological culture Collection center; the address of the depository: the institute of microbiology, national academy of sciences No. 3, Xilu No. 1, Beijing, Chaoyang, Beijing; the preservation date is as follows: 4 months and 3 days in 2014; the preservation number is: CGMCC 8994; and (3) classification and naming: penicillium sp.
Compounds 1, 2, 3 and 4 of formula I are a class of amino Sclerotiorin derivatives:
Figure 1
formula I is disclosed in the patent: sclerotiorin derivative, preparation method thereof and application thereof as antiviral agent, application date 20150624, application number 2015103686474.
The amino Sclerotiorin derivative obtained from marine fungi has extremely strong inhibitory activity on mycobacterium tuberculosis tyrosine phosphatase (mTPB), can be used for developing antitubercular medicaments, and has wide application prospect.
The invention provides an application of a compound shown in a formula I or a pharmaceutically acceptable salt thereof in preparing an anti-tuberculosis drug.
The term "pharmaceutically acceptable salts" according to the present invention refers to non-toxic inorganic or organic acid and/or base addition salts. See, e.g., "Salt selection for basic drugs", int. J. pharm. (1986), 33, 201-.
Detailed Description
In order to facilitate a further understanding of the invention, the following examples are provided to illustrate it in more detail. However, this example is only for better understanding of the invention and is not intended to limit the scope or the principle of the invention, and the embodiments of the invention are not limited to the following.
Example 1
The activity assay of the compounds of formula I of the present invention on mycobacterium tuberculosis tyrosine phosphatase (mPTPB) was tested as follows: using p-nitrophenyl phosphate (pNPP) as substrate, the reaction was carried out in 50mM 3, 3-dimethylglutarate buffer (25 ℃ C., pH 7.0). The pNPP was enzymatically hydrolyzed by mTPB to p-nitrophenol, and the activity of the enzyme was calculated by measuring the change in absorbance at a wavelength of 405nm with an ultraviolet-visible spectrophotometer. The initial reaction system is 200 muL, and comprises 5 muL of enzyme, 2.5mM of substrate pNPP and inhibitors with different concentrations, and after reacting for 15min, the absorbance value at the wavelength of 405nm is measured.
The enzyme activity was calculated using the following formula: inhibition (%) = [ (a)0-A)/A0]X 100% where A0The absorbance change value of the blank control is shown, and A is the absorbance change value of the sample. 5 samples were assayed and dose-inhibition curves were plotted to obtain IC50The value is obtained. Each sample was assayed in triplicate and the results expressed as standard deviation of the mean.
The test results show that the compounds 1, 2, 3 and 4 of the formula I have strong inhibition effect on mycobacterium tuberculosis tyrosine phosphatase (mTPB) and IC thereof50Respectively 200 mu M, 126.42 mu M, 114.55 mu M and 200 mu M.
The compound of the formula I has extremely strong inhibitory activity on mycobacterium tuberculosis tyrosine phosphatase (mTPB), and shows that the compound of the formula I or pharmaceutically acceptable salts thereof can be used for preparing antitubercular drugs, and marine fungus Penicillium sp. (TA33-1) can be subjected to large-scale fermentation production, so that the source of the compound of the formula I is ensured, and the compound of the formula I has wide application prospect.

Claims (2)

1. An antituberculous pharmaceutical composition characterized in that it comprises a compound of formula I
Figure DEST_PATH_IMAGE001
Or a pharmaceutically acceptable salt thereof, wherein R is
Figure DEST_PATH_IMAGE003
Or
Figure 527554DEST_PATH_IMAGE004
Or
Figure 788902DEST_PATH_IMAGE006
Or
Figure 240743DEST_PATH_IMAGE008
。
2. The use of a compound of formula I as claimed in claim 1 or a pharmaceutically acceptable salt thereof for the manufacture of an anti-tubercular agent.
CN201610218004.6A 2016-04-11 2016-04-11 Application of amino Sclerotiorin derivative in preparation of anti-tuberculosis drugs Active CN107286091B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610218004.6A CN107286091B (en) 2016-04-11 2016-04-11 Application of amino Sclerotiorin derivative in preparation of anti-tuberculosis drugs

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610218004.6A CN107286091B (en) 2016-04-11 2016-04-11 Application of amino Sclerotiorin derivative in preparation of anti-tuberculosis drugs

Publications (2)

Publication Number Publication Date
CN107286091A CN107286091A (en) 2017-10-24
CN107286091B true CN107286091B (en) 2020-06-19

Family

ID=60093419

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610218004.6A Active CN107286091B (en) 2016-04-11 2016-04-11 Application of amino Sclerotiorin derivative in preparation of anti-tuberculosis drugs

Country Status (1)

Country Link
CN (1) CN107286091B (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1745065A (en) * 2002-12-20 2006-03-08 沃泰克斯药物股份有限公司 4-oxo-3-(1-oxo-1h-isoquinolin-2-ylacetylamino)-pentanoic acid ester and amide derivatives and their use as aspartic specifity cysteine proteinase inhibitors
CN102603630A (en) * 2012-03-12 2012-07-25 北京科技大学 O-aminobenzoic acid sulfonylation derivative as well as preparation method and application thereof
CN105218447A (en) * 2015-06-24 2016-01-06 中国海洋大学 Sclerotiorin derivative and preparation method thereof and the application as anti-influenza A H 1 N 1 virus agent
CN105219816A (en) * 2015-06-24 2016-01-06 中国海洋大学 Sclerotiorin derivative and preparation method thereof and the application as antiviral agent

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1745065A (en) * 2002-12-20 2006-03-08 沃泰克斯药物股份有限公司 4-oxo-3-(1-oxo-1h-isoquinolin-2-ylacetylamino)-pentanoic acid ester and amide derivatives and their use as aspartic specifity cysteine proteinase inhibitors
CN102603630A (en) * 2012-03-12 2012-07-25 北京科技大学 O-aminobenzoic acid sulfonylation derivative as well as preparation method and application thereof
CN105218447A (en) * 2015-06-24 2016-01-06 中国海洋大学 Sclerotiorin derivative and preparation method thereof and the application as anti-influenza A H 1 N 1 virus agent
CN105219816A (en) * 2015-06-24 2016-01-06 中国海洋大学 Sclerotiorin derivative and preparation method thereof and the application as antiviral agent

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Bioactive azaphilones from the fungus Penicillium multicolor CM01;Hemtasin, Chulida等;《Phytochemistry Letters》;20160319;第16卷;56-60 *

Also Published As

Publication number Publication date
CN107286091A (en) 2017-10-24

Similar Documents

Publication Publication Date Title
Rauf et al. Design and synthesis of new barbituric-and thiobarbituric acid derivatives as potent urease inhibitors: Structure activity relationship and molecular modeling studies
Asai et al. A new structural class of proteasome inhibitors identified by microbial screening using yeast-based assay
US20080085918A1 (en) Fitness assay and associated methods
US20090137681A1 (en) Sirtuin Inhibiting Compounds
Sriram et al. Synthesis and Antimycobacterial Evaluation of Novel Phthalazin‐4‐ylacetamides Against log‐and Starved Phase Cultures
CN102911040B (en) Sesquiterpenoids from marine fungi source as well as preparation method and application thereof
Bringmann et al. Sorbicillactone A: a structurally unprecedented bioactive novel-type alkaloid from a sponge-derived fungus
Chintakunta et al. Synthesis, in silico studies and antibacterial activity of some novel 2-substituted benzimidazole derivatives
Zhang et al. Identification of a New Uncompetitive Inhibitor of Adenosine Deaminase from Endophyte Aspergillus niger sp.
Talukdar et al. Enhanced candicidal compound production by a new soil isolate Penicillium verruculosum MKH7 under submerged fermentation
CN109468367A (en) Aflatoxin yield detection RT-PCR kit synchronous with Nor-1 genetic transcription amount and its detection method
CN107286091B (en) Application of amino Sclerotiorin derivative in preparation of anti-tuberculosis drugs
CN103130686A (en) N,N'-asymmetric diayl substitution urea compound and preparation method and purpose thereof
Familiar et al. Exploring acyclic nucleoside analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase
CN107286120A (en) A kind of application of butyrolactone compound in antituberculotic is prepared
Harer et al. In-silico docking based design and synthesis of [1H, 3H] imidazo [4, 5-b] pyridines as lumazine synthase inhibitors for their effective antimicrobial activity
Bai et al. A high throughput screening approach to identify isocitrate lyase inhibitors from traditional Chinese medicine sources
Guo et al. Global gene expression profile of Saccharomyces cerevisiae induced by dictamnine
Murugesan et al. Antimycobacterial and phototoxic evaluation of novel 6-fluoro/nitro-4-oxo-7-(sub)-4H-[1, 3] thiazeto [3, 2-a] quinoline-3-carboxylic acid
Krstić et al. Influence of decavanadate on rat synaptic plasma membrane ATPases activity
Pang et al. Mechanism of berberine hydrochloride interfering with biofilm formation of Hafnia alvei
CN104415019B (en) 3- sulfydryl-N- benzyl Propionamides compound is inhibiting the purposes in NDM-1
Khedidja et al. Antiallergy drugs as potent inhibitors of lipase with structure-activity relationships and molecular docking
US20050251345A1 (en) Small molecules and a pharmacophore model for inhibition of anthrax lethal factor
CN106397459B (en) Thio diketopiperazine compound and its application

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant