Antimycobacterial activity of methanolic plant extract of Artemisia capillaris containing ursolic acid and hydroquinone against Mycobacterium tuberculosis

2016 ◽  
Vol 22 (4) ◽  
pp. 200-208 ◽  
Author(s):  
Md Anirban Jyoti ◽  
Kung-Woo Nam ◽  
Woong Sik Jang ◽  
Young-Hee Kim ◽  
Su-Kyung Kim ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Ursolic Acid ◽  
Plant Extract ◽  
Antimycobacterial Activity ◽  
Artemisia Capillaris

New Groups of Potential Antituberculotics: Bis(1-aryltetrazol-5-yl) Disulfides. Structure Activity Relationship

1994 ◽  
Vol 59 (1) ◽  
pp. 234-238 ◽  
Author(s):  
Karel Waisser ◽  
Jiří Kuneš ◽  
Alexandr Hrabálek ◽  
Želmíra Odlerová
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Minimum Inhibitory Concentration ◽  
Inhibitory Concentration ◽  
Antimycobacterial Activity ◽  
Activity Relationship ◽  
Active Derivative ◽  
Structure Activity ◽  
Medium Activity ◽  
Substituent Constants ◽  
Atypical Strains

Oxidation of 1-aryltetrazole-5-thiols afforded bis(1-aryltetrazol-5-yl) disulfides. The compounds were tested for antimycobacterial activity against Mycobacterium tuberculosis, M. kansasii, M. avium and M. fortuitum. In the case of M. tuberculosis, the logarithm of minimum inhibitory concentration showed a parabolic dependence on hydrophobic substituent constants. Although the compounds exhibited low to medium activity, the most active derivative, bis(4-chlorophenyltetrazol-5-yl) disulfide (III) was more effective against atypical strains than are the commercial tuberculostatics used as standards.

scholarly journals Biofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Poushali Chakraborty ◽  
Sapna Bajeli ◽  
Deepak Kaushal ◽  
Bishan Dass Radotra ◽  
Ashwani Kumar
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune System ◽  
Biofilm Formation ◽  
Antimycobacterial Activity ◽  
Drug Tolerance ◽  
Host Immune System ◽  
Tissue Sections ◽  
Slow Growing

AbstractTuberculosis is a chronic disease that displays several features commonly associated with biofilm-associated infections: immune system evasion, antibiotic treatment failures, and recurrence of infection. However, although Mycobacterium tuberculosis (Mtb) can form cellulose-containing biofilms in vitro, it remains unclear whether biofilms are formed during infection in vivo. Here, we demonstrate the formation of Mtb biofilms in animal models of infection and in patients, and that biofilm formation can contribute to drug tolerance. First, we show that cellulose is also a structural component of the extracellular matrix of in vitro biofilms of fast and slow-growing nontuberculous mycobacteria. Then, we use cellulose as a biomarker to detect Mtb biofilms in the lungs of experimentally infected mice and non-human primates, as well as in lung tissue sections obtained from patients with tuberculosis. Mtb strains defective in biofilm formation are attenuated for survival in mice, suggesting that biofilms protect bacilli from the host immune system. Furthermore, the administration of nebulized cellulase enhances the antimycobacterial activity of isoniazid and rifampicin in infected mice, supporting a role for biofilms in phenotypic drug tolerance. Our findings thus indicate that Mtb biofilms are relevant to human tuberculosis.

scholarly journals IN VITRO STUDY OF URSOLIC ACID COMBINATION FIRST-LINE ANTITUBERCULOSIS DRUGS AGAINST DRUG-SENSITIVE AND DRUG-RESISTANT STRAINS OF Mycobacterium tuberculosis

2017 ◽  
Vol 10 (4) ◽  
pp. 216 ◽  
Author(s):  
Dian Ayu Eka Pitaloka ◽  
Elin Yulinah Sukandar
Keyword(s):  
Ursolic Acid ◽  
Drug Combination ◽  
Resistant Strain ◽  
Inhibitory Concentration ◽  
In Vitro Study ◽  
Antimycobacterial Activity ◽  
Multidrug Resistant ◽  
Minimum Concentration ◽  
Different Strains

Objective: The resurgence of tuberculosis (TB) caused by Mycobacterium TB (MTB) is associated with the rapid spread of multidrug-resistant,therefore, the development of new antimycobacterial agents is necessary. The aim of this study was to evaluate the antimycobacterial activity ofursolic acid (UA) when it using alone and combination with TB drugs.Methods: MTB H37Rv strain, streptomycin-rifampicin resistant strain, and isoniazid-ethambutol resistant strain were evaluated by susceptibility testusing a serial number of UA (25-150 µg/mL). Minimum inhibitory concentration (MIC) was read as minimum concentration of drugs that completelyinhibit visible growth of organism. Activities of drug combination of UA with TB drug were determined in Lowenstein-Jensen media by calculatingthe fractional inhibitory concentration index.Results: The results showed that MIC of UA was 50 µg/mL against three different strains of MTB. The combination of UA and TB drugs displayedsynergistic interaction, and no antagonism result from the combination was observed for strains of MTB.Conclusion: These results indicate that UA may serve as a promising lead compound for future antimycobacterial drug development.Keywords: Ursolic acid, Tuberculosis, Drug combination, Susceptibility test

In vitro synergistic interactions of oleanolic acid in combination with isoniazid, rifampicin or ethambutol against Mycobacterium tuberculosis

2010 ◽  
Vol 59 (5) ◽  
pp. 567-572 ◽  
Author(s):  
Fa Ge ◽  
Fanli Zeng ◽  
Siguo Liu ◽  
Na Guo ◽  
Haiqing Ye ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Oleanolic Acid ◽  
Antimycobacterial Activity ◽  
Vero Cells ◽  
Drug Resistant ◽  
Synergistic Interactions ◽  
Combination Treatments ◽  
Low Cytotoxicity ◽  
Drug Resistant Strains

Reports have shown that oleanolic acid (OA), a triterpenoid, exists widely in food, medicinal herbs and other plants, and that it has antimycobacterial activity against the Mycobacterium tuberculosis strain H37Rv (ATCC 27294). In this study it was found that OA had antimycobacterial properties against eight clinical isolates of M. tuberculosis and that the MICs of OA against drug-sensitive and drug-resistant isolates were 50–100 and 100–200 μg ml−1, respectively. The combination of OA with isoniazid (INH), rifampicin (RMP) or ethambutol (EMB) showed favourable synergistic antimycobacterial effects against six drug-resistant strains, with fractional inhibitory concentration indices of 0.121–0.347, 0.113–0.168 and 0.093–0.266, respectively. The combination treatments of OA/INH, OA/RMP and OA/EMB displayed either a synergistic interaction or did not show any interaction against two drug-sensitive strains. No antagonism resulting from the OA/INH, OA/RMP or OA/EMB combination was observed for any of the strains tested. OA exhibited a relatively low cytotoxicity in Vero cells. These results indicate that OA may serve as a promising lead compound for future antimycobacterial drug development.

scholarly journals Ambroxol Induces Autophagy and Potentiates Rifampin Antimycobacterial Activity

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Seong Won Choi ◽  
Yuexi Gu ◽  
Ryan Scott Peters ◽  
Padmini Salgame ◽  
Jerrold J. Ellner ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antimycobacterial Activity ◽  
Lead Compound ◽  
Content Type ◽  
Tuberculosis Model

ABSTRACT Host-directed therapy in tuberculosis is a potential adjunct to antibiotic chemotherapy directed at Mycobacterium tuberculosis. Ambroxol, a lead compound, emerged from a screen for autophagy-inducing drugs. At clinically relevant doses, ambroxol induced autophagy in vitro and in vivo and promoted mycobacterial killing in macrophages. Ambroxol also potentiated rifampin activity in a murine tuberculosis model.

scholarly journals Secondary metabolites from Triclisia gilletii (De Wild) Staner (Menispermaceae) with antimycobacterial activity against Mycobacterium tuberculosis

2017 ◽  
Vol 33 (5) ◽  
pp. 642-650 ◽  
Author(s):  
Eric Robert Tiam ◽  
Dominique Serge Ngono Bikobo ◽  
Auguste Abouem A Zintchem ◽  
Norbert Mbabi Nyemeck ◽  
Esther Del Florence Moni Ndedi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Secondary Metabolites ◽  
Antimycobacterial Activity

scholarly journals The 8-Pyrrole-Benzothiazinones Are Noncovalent Inhibitors of DprE1 from Mycobacterium tuberculosis

2015 ◽  
Vol 59 (8) ◽  
pp. 4446-4452 ◽  
Author(s):  
Vadim Makarov ◽  
João Neres ◽  
Ruben C. Hartkoorn ◽  
Olga B. Ryabova ◽  
Elena Kazakova ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Nitro Group ◽  
Covalent Bond ◽  
Antimycobacterial Activity ◽  
Content Type ◽  
Sar Studies ◽  
Covalent Bond Formation

ABSTRACT8-Nitro-benzothiazinones (BTZs), such as BTZ043 and PBTZ169, inhibit decaprenylphosphoryl-β-d-ribose 2′-oxidase (DprE1) and display nanomolar bactericidal activity againstMycobacterium tuberculosisin vitro. Structure-activity relationship (SAR) studies revealed the 8-nitro group of the BTZ scaffold to be crucial for the mechanism of action, which involves formation of a semimercaptal bond with Cys387 in the active site of DprE1. To date, substitution of the 8-nitro group has led to extensive loss of antimycobacterial activity. Here, we report the synthesis and characterization of the pyrrole-benzothiazinones PyrBTZ01 and PyrBTZ02, non-nitro-benzothiazinones that retain significant antimycobacterial activity, with MICs of 0.16 μg/ml againstM. tuberculosis. These compounds inhibit DprE1 with 50% inhibitory concentration (IC50) values of <8 μM and present favorablein vitroabsorption-distribution-metabolism-excretion/toxicity (ADME/T) andin vivopharmacokinetic profiles. The most promising compound, PyrBTZ01, did not show efficacy in a mouse model of acute tuberculosis, suggesting that BTZ-mediated killing through DprE1 inhibition requires a combination of both covalent bond formation and compound potency.

scholarly journals Bazedoxifene Suppresses Intracellular Mycobacterium tuberculosis Growth by Enhancing Autophagy

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Qi Ouyang ◽  
Kehong Zhang ◽  
Dachuan Lin ◽  
Carl G. Feng ◽  
Yi Cai ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antimycobacterial Activity ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
New Host ◽  
Drug Resistant Tuberculosis ◽  
Content Type ◽  
Receptor Modulator ◽  
Resistant Tuberculosis ◽  
Negative Side Effects

ABSTRACT Tuberculosis (TB) is still the leading killer caused by Mycobacterium tuberculosis infection. There is a clear need for new treatment strategy against TB. It has been reported that tamoxifen, known as a selective estrogen receptor modulator (SERM), exhibits antimycobacterial activity and inhibits M. tuberculosis growth in macrophages. However, it remains unknown whether such antimicrobial activity is a general property of all SERMs and how it works. In this study, we identified that bazedoxifene (BZA), a newer SERM, inhibits intracellular M. tuberculosis growth in macrophages. BZA treatment increases autophagosome formation and LC3B-II protein expression in M. tuberculosis-infected macrophages. We further demonstrated that the enhancement of autophagy by BZA is dependent on increased reactive oxygen species (ROS) production and associated with phosphorylation of Akt/mTOR signaling. In summary, our data reveal a previously unappreciated antimicrobial function of BZA and suggest that future investigation focusing on the mechanism of action of SERMs in macrophages may lead to new host-directed therapies against TB. IMPORTANCE Since current strategies for the treatment of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) have low efficacy and highly negative side effects, research on new treatments including novel drugs is essential for curing drug-resistant tuberculosis. Host-directed therapy (HDT) has become a promising idea to modulate host cell responses to enhance protective immunity against pathogens. Bazedoxifene (BZA), which belongs to a new generation of SERMs, shows the ability to inhibit the growth of M. tuberculosis in macrophages and is associated with autophagy. Our findings reveal a previously unrecognized antibacterial function of BZA. We propose that the mechanism of SERMs action in macrophages may provide a new potential measure for host-directed therapies against TB.

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