scholarly journals Mode of Action of Kanglemycin A, an Ansamycin Natural Product that Is Active against Rifampicin-Resistant Mycobacterium tuberculosis

2018 ◽  
Vol 72 (2) ◽  
pp. 263-274.e5 ◽  
Author(s):  
Hamed Mosaei ◽  
Vadim Molodtsov ◽  
Bernhard Kepplinger ◽  
John Harbottle ◽  
Christopher William Moon ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Natural Product ◽  
Mode Of Action

scholarly journals Recent Advances in Mode of Action and Biosynthesis Studies of the Clinically Used Antibiotic Fidaxomicin

2020 ◽  
Vol 74 (4) ◽  
pp. 270-273 ◽  
Author(s):  
Andrea Dorst ◽  
Erik Jung ◽  
Karl Gademann
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Natural Product ◽  
Mode Of Action ◽  
Bacterial Infections ◽  
Biosynthetic Pathway ◽  
Antibacterial Activities ◽  
Next Generation ◽  
Unique Mode ◽  
Recent Advances

The natural product antibiotic fidaxomicin is a marketed drug for the treatment of bacterial infections in the gut. Due to its promising in vitro activities against Mycobacterium tuberculosis, the development of next generation fidaxomicin analogs is of great interest. This article reviews the most recent advances, including the elucidation of a unique mode of action by cryo-EM structures, and the efforts towards the clarification of the biosynthetic pathway. Moreover, known fidaxomicin analogs and their reported antibacterial activities are summarized.

Natural product growth inhibitors of Mycobacterium tuberculosis

2007 ◽  
Vol 24 (2) ◽  
pp. 278-297 ◽  
Author(s):  
Brent R. Copp ◽  
A. Norrie Pearce
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Natural Product ◽  
Growth Inhibitors

scholarly journals Stereocontrolled Total Synthesis of Muraymycin D1 Having a Dual Mode of Action against Mycobacterium tuberculosis

2016 ◽  
Vol 138 (39) ◽  
pp. 12975-12980 ◽  
Author(s):  
Katsuhiko Mitachi ◽  
Bilal A. Aleiwi ◽  
Christopher M. Schneider ◽  
Shajila Siricilla ◽  
Michio Kurosu
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Total Synthesis ◽  
Mode Of Action ◽  
Dual Mode

scholarly journals A Phenotarget Approach for Identifying an Alkaloid Interacting with the Tuberculosis Protein Rv1466

Marine Drugs ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 149 ◽  
Author(s):  
Yan Xie ◽  
Yunjiang Feng ◽  
Angela Di Capua ◽  
Tin Mak ◽  
Garry W. Buchko ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Mycobacterium Tuberculosis ◽  
Drug Discovery ◽  
Natural Product ◽  
Covalent Bond ◽  
Pure Compound ◽  
Active Components ◽  
Ligand Complex ◽  
Mycobacterium Tuberculosis H37rv ◽  
Compound Libraries

In recent years, there has been a revival of interest in phenotypic-based drug discovery (PDD) due to target-based drug discovery (TDD) falling below expectations. Both PDD and TDD have their unique advantages and should be used as complementary methods in drug discovery. The PhenoTarget approach combines the strengths of the PDD and TDD approaches. Phenotypic screening is conducted initially to detect cellular active components and the hits are then screened against a panel of putative targets. This PhenoTarget protocol can be equally applied to pure compound libraries as well as natural product fractions. Here we described the use of the PhenoTarget approach to identify an anti-tuberculosis lead compound. Fractions from Polycarpa aurata were identified with activity against Mycobacterium tuberculosis H37Rv. Native magnetic resonance mass spectrometry (MRMS) against a panel of 37 proteins from Mycobacterium proteomes showed that a fraction from a 95% ethanol re-extraction specifically formed a protein-ligand complex with Rv1466, a putative uncharacterized Mycobacterium tuberculosis protein. The natural product responsible was isolated and characterized to be polycarpine. The molecular weight of the ligand bound to Rv1466, 233 Da, was half the molecular weight of polycarpine less one proton, indicating that polycarpine formed a covalent bond with Rv1466.

scholarly journals Mode of action of a fatty acid-based natural product to control Botrytis cinerea in grapes

2014 ◽  
Vol 116 (4) ◽  
pp. 967-979 ◽  
Author(s):  
C. Calvo-Garrido ◽  
P.A.G. Elmer ◽  
F.J. Parry ◽  
I. Viñas ◽  
J. Usall ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Natural Product ◽  
Botrytis Cinerea ◽  
Mode Of Action

scholarly journals Synthesis and anti-tubercular activity of 3-substituted benzothiophene-1,1-dioxides

2014 ◽  
Author(s):  
N. Susantha Chandrasekera ◽  
Mai A Bailey ◽  
Megan Files ◽  
Torey Alling ◽  
Stephanie K Florio ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Minimum Inhibitory Concentration ◽  
Mode Of Action ◽  
Drug Targets ◽  
Inhibitory Concentration ◽  
Eukaryotic Cells ◽  
Structure Activity ◽  
Novel Drug ◽  
Further Development ◽  
Novel Drug Targets

We demonstrated that the 3-substituted benzothiophene-1,1-dioxide class of compounds are effective inhibitors of Mycobacterium tuberculosis growth under aerobic conditions. We examined substitution at the C-3 position of the benzothiophene-1,1-dioxide series systematically to delineate structure-activity relationships influencing potency and cytotoxicity. Compounds were tested for inhibitory activity against virulent M. tuberculosis and eukaryotic cells. The tetrazole substituent was most potent, with a minimum inhibitory concentration (MIC) of 2.6 µM. However, cytotoxicity was noted with even more potency (Vero cell TC50 = 0.1 µM). Oxadiazoles had good anti-tubercular activity (MICs of 3–8 µM), but imidazoles, thiadiazoles and thiazoles had little activity. Cytotoxicity did not track with anti-tubercular activity, suggesting different targets or mode of action between bacterial and eukaryotic cells. However, we were unable to derive analogs without cytotoxicity; all compounds synthesized were cytotoxic (TC50 of 0.1–5 µM). We conclude that cytotoxicity is a liability in this series precluding it from further development. However, the series has potent anti-tubercular activity and future efforts towards identifying the mode of action could result in the identification of novel drug targets.

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