• 제목/요약/키워드: Antimycobacterial

검색결과 20건 처리시간 0.018초

Antimicrobial Peptides in Innate Immunity against Mycobacteria

  • Shin, Dong-Min;Jo, Eun-Kyeong
    • IMMUNE NETWORK
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    • 제11권5호
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    • pp.245-252
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    • 2011
  • Antimicrobial peptides/proteins are ancient and naturally-occurring antibiotics in innate immune responses in a variety of organisms. Additionally, these peptides have been recognized as important signaling molecules in regulation of both innate and adaptive immunity. During mycobacterial infection, antimicrobial peptides including cathelicidin, defensin, and hepcidin have antimicrobial activities against mycobacteria, making them promising candidates for future drug development. Additionally, antimicrobial peptides act as immunomodulators in infectious and inflammatory conditions. Multiple crucial functions of cathelicidins in antimycobacterial immune defense have been characterized not only in terms of direct killing of mycobacteria but also as innate immune regulators, i.e., in secretion of cytokines and chemokines, and mediating autophagy activation. Defensin families are also important during mycobacterial infection and contribute to antimycobacterial defense and inhibition of mycobacterial growth both in vitro and in vivo. Hepcidin, although its role in mycobacterial infection has not yet been characterized, exerts antimycobacterial effects in activated macrophages. The present review focuses on recent efforts to elucidate the roles of host defense peptides in innate immunity to mycobacteria.

Antimycobacterial and Antioxidant Flavones from Limnophila geoffrayi

  • Suksamrarn, Apichart;Poomsing, Ponsuda;Aroonrerk, Nuntana;Punjanon, Tadsanee;Suksamrarn, Sunit;Kongkun, Somkiat
    • Archives of Pharmacal Research
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    • 제26권10호
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    • pp.816-820
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    • 2003
  • The chloroform extract of the aerial part of Limnophila geoffrayi showed antimycobacterial and antioxidant activities. Bioassay-guided fractionation has led to the isolation of the flavones nevadensin (5,7-dihydroxy-6,8,4'-trimethoxyflavone, 1) and isothymusin (6,7-dimethoxy-5,8,4'-trihydroxyflavone, 2). Both compounds 1 and 2 exhibited inhibition activity against Mycobacterium tuberculosis, with equal MIC value of $200{\;}\mu\textrm{g}/mL$. Only compound 2 exhibited antioxidant activity against the radical scavenging ability of DPPH, with the $IC_{50}$ value of $7.7{\;}\mu\textrm{g}/mL$. The crude hexane, chloroform and methanol extracts as well as the pure compounds 1 and 2 did not exhibit mutagenic activity in the Bacillus subtilis recassay.

Antimycobacterial Activity and Cytotoxicity of Flavonoids from the Flowers of Chromolaena odorata

  • Suksamrarn, Apichart;Chotipong, Apinya;Suavansri, Tananit;Boongird, Somnuk;Timsuksai, Puntip;Vimuttipong, Saovaluk;Chuaynugul, Aporn
    • Archives of Pharmacal Research
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    • 제27권5호
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    • pp.507-511
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    • 2004
  • From the flowers of Chromolaena odorata (Eupatorium odoratum) four flavanones, isosakuranetin (5,7-dihydroxy-4'-methoxyflavanone) (1), persicogenin (5,3'-dihydroxy-7,4'-dimethoxyflavanone) (2), 5,6,7,4'-tetramethoxyflavanone (3) and 4'-hydroxy-5,6,7-trimethoxyfla-vanone (4), two chalcones, 2'-hydroxy-4,4',5',6'-tetramethoxychalcone (5) and 4,2'-dihydroxy-4',5',6'-trimethoxychalcone (6), and two flavones, acacetin (5,7-dihydroxy-4'-methoxyflavone) (7) and luteolin (5,7,3',4'-tetrahydroxyflavone) (8) were isolated and identified. Compound 1 exhibited moderate antimycobacterial activity against Mycobacterium tuberculosis with the MIC value of 174.8 $\mu$M, whereas compounds 4,7, and 8 exhibited weak activity with the MIC values of 606.0, 704.2 and 699.3 $\mu$M respectively. Compound 7 showed moderate cytotoxicity against human small cell lung cancer (NCI-H187) cells with the MIC value of 24.6 $\mu$M, whereas compound 8 exhibited moderate toxicity against NCI-H187 cells and week toxicity against human breast cancer (BC) cells with the MIC values of 19.2 and 38.4 $\mu$M respectively.

Design and Synthesis of p-hydroxybenzohydrazide Derivatives for their Antimycobacterial Activity

  • Bhole, Ritesh.P.;Borkar, Deepak.D.;Bhusari, Kishore.P.;Patil, Prashant.A.
    • 대한화학회지
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    • 제56권2호
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    • pp.236-245
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    • 2012
  • The main mycobacterial infection in human is tuberculosis caused by Mycobacterium tuberculosis. Tuberculosis is the leading infectious cause of death in the world. Therefore there is continuing and compelling need for new and improved treatment for tuberculosis. The entire logic towards design of new compounds containing 4-hydroxy-N'-(1,3-thiazoldin- 2-yldene)benzohydrazide moiety is basically for superior antimycobacterial activity. The recent advances in QSAR and computer science have provided a systematic approach to design a structure of any compound and further, the biological activity of the compound can be predicted before synthesis. The 3D-QSAR studies for the set of 4-hydroxy-N'-(1,3-thiazoldin- 2-yldene)benzohydrazide and their derivatives were carried out by using V-life MDS (3.50). The various statistical methods such as Multiple Linear Regression (MLR), Partial Least Square Regression (PLSR), Principle Component Regression(PCR) and K nearest neighbour (kNN) were used. The kNN showed good results having cross validated $r^2$ 0.9319, $r^2$ for external test set 0.8561 and standard error of estimate 0.2195. The docking studies were carried out by using Schrodinger GLIDE module which resulted in good docking score in comparison with the standard isoniazid. The designed compounds were further subjected for synthesis and biological evaluation. Antitubercular evaluation of these compounds showed that (4.a), (4.d) and (4.g) found as potent inhibitor of H37RV.

환삼덩굴(Humulus japonicus) 추출물의 항결핵 효과 (Anti-mycobacterial Effects of the Extract of Humulus japonicus)

  • 홍민선;손은순;이성중;이선경;이예진;송선대;조상래;크립톤 베리;엄석용
    • 한국식품과학회지
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    • 제46권1호
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    • pp.94-99
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    • 2014
  • 환삼덩굴의 항결핵효능을 알아보기 위하여 두 가지의 실험을 실시하였다. 먼저 환삼덩굴의 메탄올 추출물을 만들어 결핵균에 직접 작용시켰을 때 아주 우수한 결핵균살상효과를 보였다. 두번째로 탐식구에 감염된 결핵균에 대한 증식 억제효능이 있는지 알아 보기 위해 사람의 대식구에 메탄올 추출물을 작용시킨 후 결핵균을 감였시켰을 때 대조군에 비해 현저한 결핵균 증식억제 효과를 보였다. 환삼덩굴의 메탄올 추출물로부터 여러가지 용매를 통해 다섯 가지의 분획물을 얻어 같은 실험을 실시하였다. 이들 분획물 중 결핵균 직접 살상효과를 보인 것은 헥산과 에틸아세테이트층이었고, 탐식구에 감염된 결핵균에 대한 증식억제 효능을 보인 것은 부탄올과 물층이었다. 이처럼 환삼덩굴은 결핵균에 대해 직접적인 살상효과 뿐 아니라 탐식구에 감염되어 있는 결핵균의 증식을 억제하는 효과도 보여 주었는데 이와 같은 결과로 볼 때 환삼덩굴로부터 새로운 결핵치료물질 개발을 기대해 볼 수 있을 것으로 기대된다.

면역 저하 환자에서 발생한 파종성 Mycobacterium intracellulare 감염 1예 (A Case of Disseminated Mycobacterium intracellulare Infection in an Immunocompromised Host)

  • 김선영;오동욱;유지희;김동회;노세희;노재형;정상수;유동준;심태선
    • Tuberculosis and Respiratory Diseases
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    • 제67권1호
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    • pp.32-36
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    • 2009
  • 본 증례는 AIDS가 아닌 면역저하 환자에서 M. intracellulare에 의하여 관절염 및 흉수가 발생한 파종성 질환의 예로 국내에서 두 번째로 보고되는 바이다.

Anti-Mycobacterial Activity of Tamoxifen Against Drug-Resistant and Intra-Macrophage Mycobacterium tuberculosis

  • Jang, Woong Sik;Kim, Sukyung;Podder, Biswajit;Jyoti, Md. Anirban;Nam, Kung-Woo;Lee, Byung-Eui;Song, Ho-Yeon
    • Journal of Microbiology and Biotechnology
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    • 제25권6호
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    • pp.946-950
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    • 2015
  • Recently, it has become a struggle to treat tuberculosis with the current commercial antituberculosis drugs because of the increasing emergence of multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis. We evaluated here the antimycobacterial activity of tamoxifen, known as a synthetic anti-estrogen, against eight drugsensitive or resistant strains of Mycobacterium tuberculosis (TB), and the active intracellular killing of tamoxifen on TB in macrophages. The results showed that tamoxifen had antituberculosis activity against drug-sensitive strains (MIC, 3.125-6.25 µg/ml) as well as drugresistant strains (MIC, 6.25 to 12.5 µg/ml). In addition, tamoxifen profoundly decreased the number of intracellular TB in macrophages in a dose-dependent manner.

The Role of Nitric Oxide in Mycobacterial Infections

  • Yang, Chul-Su;Yuk, Jae-Min;Jo, Eun-Kyeong
    • IMMUNE NETWORK
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    • 제9권2호
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    • pp.46-52
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    • 2009
  • Although tuberculosis poses a significant health threat to the global population, it is a challenge to develop new and effective therapeutic strategies. Nitric oxide (NO) and inducible NO synthase (iNOS) are important in innate immune responses to various intracellular bacterial infections, including mycobacterial infections. It is generally recognized that reactive nitrogen intermediates play an effective role in host defense mechanisms against tuberculosis. In a murine model of tuberculosis, NO plays a crucial role in antimycobacterial activity; however, it is controversial whether NO is critically involved in host defense against Mycobacterium tuberculosis in humans. Here, we review the roles of NO in host defense against murine and human tuberculosis. We also discuss the specific roles of NO in the central nervous system and lung epithelial cells during mycobacterial infection. A greater understanding of these defense mechanisms in human tuberculosis will aid in the development of new strategies for the treatment of disease.

Synthesis, Antitubercular Activity and Pharmacokinetic Studies of Some Schiff Bases Derived from 1-Alkylisatin and Isonicotinic Acid Hydrazide (INH)

  • Tarek, Aboul-Fadl;Mohammed, Faragany Abdel-Hamid;Hassan, Ehsan Abdel-Saboor
    • Archives of Pharmacal Research
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    • 제26권10호
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    • pp.778-784
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    • 2003
  • N'-(1-alkyl-2,3-dihydro-2-oxo-1H-3-indolyliden)-4-pyridinecarboxylic acid hydrazide derivatives, 3(a-g), were synthesized in a trial to overcome the resistance developed with the therapeutic uses of isoniazid (INH). The lipophilicity of the synthesized derivatives supersedes that of the INH as expressed by Clog p values. The synthesized compounds and INH were tested against bovin, human sensitive and human resist strains of Mycobacterium tuberculosis. Compounds 3a, 3d, 3f and 3g with 1-unsubstituted, 1-propyl, 1-propynyl and 1-benzyl groups respectively exhibited equipotent growth inhibitory activity (MIC 10 $\mu$mol) against the tested strains as compared with INH however the later has no activity against human resist strain. Pharmacokinetic study revealed that the rate and extent of absorption of the tested derivatives (3d and 3f) significantly higher than that of INH (p<0.05). The relative bioavailabilities ($F_R%$) were 183.15 and 443.25 for 3f and 3d respectively as compared to INH. These results preliminary indicate the possible use of the prepared derivatives for treatment of tuberculosis infections in order to overcome the resistance developed with INH.

Ursolic Acid Activates Intracellular Killing Effect of Macrophages During Mycobacterium tuberculosis Infection

  • Podder, Biswajit;Jang, Woong Sik;Nam, Kung-Woo;Lee, Byung-Eui;Song, Ho-Yeon
    • Journal of Microbiology and Biotechnology
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    • 제25권5호
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    • pp.738-744
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    • 2015
  • Tuberculosis is one of the most threatening infectious diseases to public health all over the world, for which Mycobacterium tuberculosis (MTB) is the etiological agent of pathogenesis. Ursolic acid (UA) has immunomodulatory function and exhibits antimycobacterial activity. However, the intracellular killing effect of UA has yet to be elucidated. The aim of this study was to evaluate the intracellular killing effect of UA during mycobacterial infection. The intracellular killing activity of UA was evaluated in the macrophage cell line THP-1 by the MGIT 960 system as well as by CFU count. The production of reactive oxygen species (ROS) and the level of nitric oxide (NO) were measured using DCF-DA and Griess reagent, respectively. Phagocytosis was observed by a fluorescence-based staining method, and the colony forming units were enumerated on 7H11 agar medium following infection. In addition, MRP8 mRNA expression was measured by qRT-PCR. UA significantly decreased the number of intracellular Mycobacterium through generation of ROS and NO. In addition, it profoundly activated the phagocytosis process of THP-1 cells during MTB-infection. Furthermore, our data demonstrated that UA activated the phagocytosis process in human monocyte cells through MRP8 induction. These data suggest that UA firmly contributes to the intracellular killing effect of macrophages during mycobacterial infection.