Full Text Journal Articles by
Author Helena I Boshoff

Advertisement

Find full text journal articles






Structure-aided optimization of non-nucleoside M. tuberculosis thymidylate kinase inhibitors.

Lijun Song, Romain Merceron, Fabian Hulpia, Ainhoa Lucía, Begoña Gracia, Yanlin Jian, Martijn D P Risseeuw, Toon Verstraelen, Paul Cos, José A Aínsa, Helena I Boshoff, Hélène Munier-Lehmann, Savvas N Savvides, Serge Van Calenbergh,

Mycobacterium tuberculosis thymidylate kinase (MtTMPK) has emerged as an attractive target for rational drug design. We recently investigated new families of non-nucleoside MtTMPK inhibitors in an effort to diversify MtTMPK inhibitor chemical space. We here report a new series of MtTMPK inhibitors by combining the Topliss scheme with rational drug ... Read more >>

Eur J Med Chem (European journal of medicinal chemistry)
[2021, 225:113784]

Cited: 0 times

View full text PDF listing >>



1,3-Diarylpyrazolyl-acylsulfonamides as Potent Anti-tuberculosis Agents Targeting Cell Wall Biosynthesis in Mycobacterium tuberculosis.

Lutete Peguy Khonde, Rudolf Müller, Grant A Boyle, Virsinha Reddy, Aloysius T Nchinda, Charles J Eyermann, Stephen Fienberg, Vinayak Singh, Alissa Myrick, Efrem Abay, Mathew Njoroge, Nina Lawrence, Qin Su, Timothy G Myers, Helena I M Boshoff, Clifton E Barry, Frederick A Sirgel, Paul D van Helden, Lisa M Massoudi, Gregory T Robertson, Anne J Lenaerts, Gregory S Basarab, Sandeep R Ghorpade, Kelly Chibale,

Phenotypic whole cell high-throughput screening of a ∼150,000 diverse set of compounds against <i>Mycobacterium tuberculosis</i> (Mtb) in cholesterol-containing media identified 1,3-diarylpyrazolyl-acylsulfonamide <b>1</b> as a moderately active hit. Structure-activity relationship (SAR) studies demonstrated a clear scope to improve whole cell potency to MIC values of <0.5 μM, and a plausible pharmacophore ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2021, 64(17):12790-12807]

Cited: 0 times

View full text PDF listing >>



Advertisement

The Tuberculosis Drug Accelerator at year 10: what have we learned?

Bree B Aldridge, David Barros-Aguirre, Clifton E Barry, Robert H Bates, Steven J Berthel, Helena I Boshoff, Kelly Chibale, Xin-Jie Chu, Christopher B Cooper, Véronique Dartois, Ken Duncan, Nader Fotouhi, Fabian Gusovsky, Philip A Hipskind, Dale J Kempf, Joël Lelièvre, Anne J Lenaerts, Case W McNamara, Valerie Mizrahi, Carl Nathan, David B Olsen, Tanya Parish, H Michael Petrassi, Alexander Pym, Kyu Y Rhee, Gregory T Robertson, Jeremy Michael Rock, Eric J Rubin, Betsy Russell, David G Russell, James C Sacchettini, Dirk Schnappinger, Michael Schrimpf, Anna M Upton, Peter Warner, Paul Graham Wyatt, Ying Yuan,

Nat Med (Nature medicine)
[2021, 27(8):1333-1337]

Cited: 1 time

View full text PDF listing >>



6-Fluorophenylbenzohydrazides inhibit Mycobacterium tuberculosis growth through alteration of tryptophan biosynthesis.

Sara Consalvi, Giulia Venditti, Junhao Zhu, Helena I Boshoff, Kriti Arora, Alessandro De Logu, Thomas R Ioerger, Eric J Rubin, Mariangela Biava, Giovanna Poce,

A major constraint in reducing tuberculosis epidemic is the emergence of strains resistant to one or more of clinically approved antibiotics, which emphasizes the need of novel drugs with novel targets. Genetic knockout strains of Mycobacterium tuberculosis (Mtb) have established that tryptophan (Trp) biosynthesis is essential for the bacterium to ... Read more >>

Eur J Med Chem (European journal of medicinal chemistry)
[2021, 226:113843]

Cited: 0 times

View full text PDF listing >>



Reinvestigation of the structure-activity relationships of isoniazid.

Pooja Hegde, Helena I M Boshoff, Yudi Rusman, Wassihun Wedajo Aragaw, Christine E Salomon, Thomas Dick, Courtney C Aldrich,

Isoniazid (INH) remains a cornerstone for treatment of drug susceptible tuberculosis (TB), yet the quantitative structure-activity relationships for INH are not well documented in the literature. In this paper, we have evaluated a systematic series of INH analogs against contemporary Mycobacterium tuberculosis strains from different lineages and a few non-tuberculous ... Read more >>

Tuberculosis (Edinb) (Tuberculosis (Edinburgh, Scotland))
[2021, 129:102100]

Cited: 0 times

View full text PDF listing >>



Tuberculosis Drug Discovery: A Decade of Hit Assessment for Defined Targets.

Sangmi Oh, Lena Trifonov, Veena D Yadav, Clifton E Barry, Helena I Boshoff,

More than two decades have elapsed since the publication of the first genome sequence of <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) which, shortly thereafter, enabled methods to determine gene essentiality in the pathogen. Despite this, target-based approaches have not yielded drugs that have progressed to clinical testing. Whole-cell screening followed by elucidation of ... Read more >>

Front Cell Infect Microbiol (Frontiers in cellular and infection microbiology)
[2021, 11:611304]

Cited: 1 time

View full text PDF listing >>



Determining Minimum Inhibitory Concentrations in Liquid Cultures or on Solid Medium.

Qinglan Wang, Helena I M Boshoff,

Antimicrobial susceptibility testing is the mainstay of tuberculosis drug development programs. In this chapter, we describe methods for determination of the minimum inhibitory concentration of compounds against Mycobacterium tuberculosis growing in liquid media as a function of carbon source, detergent, and environmental stress imposed by acidic pH as well as ... Read more >>

Methods Mol Biol (Methods in molecular biology (Clifton, N.J.))
[2021, 2314:595-609]

Cited: 0 times

View full text PDF listing >>



Development and Optimization of Chromosomally-Integrated Fluorescent Mycobacterium tuberculosis Reporter Constructs.

Katharina Kolbe, Alice C Bell, Gareth A Prosser, Maike Assmann, Hee-Jeong Yang, He Eun Forbes, Sophia Gallucci, Katrin D Mayer-Barber, Helena I Boshoff, Clifton E Barry Iii,

<i>Mycobacterium tuberculosis</i> resides in the lungs in various lesion types with unique microenvironmental conditions. This diversity is in line with heterogeneous disease progression and divergent drug efficiency. Fluorescent reporter strains can be used to decipher the micromilieu and to guide future treatment regimens. Current reporters using replicating plasmids, however, are ... Read more >>

Front Microbiol (Frontiers in microbiology)
[2020, 11:591866]

Cited: 0 times

View full text PDF listing >>



Correction for Singh et al., "The Three RelE Homologs of Mycobacterium tuberculosis Have Individual, Drug-Specific Effects on Bacterial Antibiotic Tolerance".

Ramandeep Singh, Clifton E Barry, Helena I M Boshoff,

J Bacteriol (Journal of bacteriology)
[2020, 202(24):]

Cited: 0 times

View full text PDF listing >>



2-((3,5-Dinitrobenzyl)thio)quinazolinones: Potent Antimycobacterial Agents Activated by Deazaflavin (F420)-Dependent Nitroreductase (Ddn).

Yanlin Jian, He Eun Forbes, Fabian Hulpia, Martijn D P Risseeuw, Guy Caljon, Hélène Munier-Lehmann, Helena I M Boshoff, Serge Van Calenbergh,

Swapping the substituents in positions 2 and 4 of the previously synthesized but yet undisclosed 5-cyano-4-(methylthio)-2-arylpyrimidin-6-ones <b>4</b>, ring closure, and further optimization led to the identification of the potent antitubercular 2-thio-substituted quinazolinone <b>26</b>. Structure-activity relationship (SAR) studies indicated a crucial role for both <i>meta</i>-nitro substituents for antitubercular activity, while the ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2021, 64(1):440-457]

Cited: 0 times

View full text PDF listing >>



Tissue specific diversification, virulence and immune response to Mycobacterium bovis BCG in a patient with an IFN-γ R1 deficiency.

Cecilia B Korol, Shamira J Shallom, Kriti Arora, Helena I Boshoff, Alexandra F Freeman, Alejandra King, Sonia Agrawal, Sean C Daugherty, Timothy Jancel, Juraj Kabat, Sundar Ganesan, Marina N Torrero, Elizabeth P Sampaio, Clifton Barry, Steve M Holland, Hervé Tettelin, Sergio D Rosenzweig, Adrian M Zelazny,

<b>Summary</b>: We characterized <i>Mycobacterium bovis</i> BCG isolates found in lung and brain samples from a previously vaccinated patient with IFNγR1 deficiency. The isolates collected displayed distinct genomic and phenotypic features consistent with host adaptation and associated changes in antibiotic susceptibility and virulence traits. <b>Background</b>: We report a case of a ... Read more >>

Virulence (Virulence)
[2020, 11(1):1656-1673]

Cited: 0 times

View full text PDF listing >>



Endeavors towards transformation of M. tuberculosis thymidylate kinase (MtbTMPK) inhibitors into potential antimycobacterial agents.

Yanlin Jian, Romain Merceron, Steven De Munck, He Eun Forbes, Fabian Hulpia, Martijn D P Risseeuw, Kristof Van Hecke, Savvas N Savvides, Hélène Munier-Lehmann, Helena I M Boshoff, Serge Van Calenbergh,

As the last enzyme in nucleotide synthesis as precursors for DNA replication, thymidylate kinase of M. tuberculosis (MtbTMPK) attracts significant interest as a target in the discovery of new anti-tuberculosis agents. Earlier, we discovered potent MtbTMPK inhibitors, but these generally suffered from poor antimycobacterial activity, which we hypothesize is due to ... Read more >>

Eur J Med Chem (European journal of medicinal chemistry)
[2020, 206:112659]

Cited: 0 times

View full text PDF listing >>



Development of small-molecule inhibitors of fatty acyl-AMP and fatty acyl-CoA ligases in Mycobacterium tuberculosis.

Marzena Baran, Kimberly D Grimes, Paul A Sibbald, Peng Fu, Helena I M Boshoff, Daniel J Wilson, Courtney C Aldrich,

Lipid metabolism in Mycobacterium tuberculosis (Mtb) relies on 34 fatty acid adenylating enzymes (FadDs) that can be grouped into two classes: fatty acyl-CoA ligases (FACLs) involved in lipid and cholesterol catabolism and long chain fatty acyl-AMP ligases (FAALs) involved in biosynthesis of the numerous essential and virulence-conferring lipids found in ... Read more >>

Eur J Med Chem (European journal of medicinal chemistry)
[2020, 201:112408]

Cited: 3 times

View full text PDF listing >>



Synthesis and structure activity relationships of cyanopyridone based anti-tuberculosis agents.

Yanlin Jian, Fabian Hulpia, Martijn D P Risseeuw, He Eun Forbes, Hélène Munier-Lehmann, Guy Caljon, Helena I M Boshoff, Serge Van Calenbergh,

Mycobacterium tuberculosis, the causative agent of tuberculosis, relies on thymidylate kinase (MtbTMPK) for the synthesis of thymidine triphosphates and thus also DNA synthesis. Therefore, this enzyme constitutes a potential Achilles heel of the pathogen. Based on a previously reported MtbTMPK 6-aryl-substituted pyridone inhibitor and guided by two co-crystal structures of ... Read more >>

Eur J Med Chem (European journal of medicinal chemistry)
[2020, 201:112450]

Cited: 0 times

View full text PDF listing >>



PE/PPE proteins mediate nutrient transport across the outer membrane of Mycobacterium tuberculosis.

Qinglan Wang, Helena I M Boshoff, Justin R Harrison, Peter C Ray, Simon R Green, Paul G Wyatt, Clifton E Barry,

Mycobacterium tuberculosis has an unusual outer membrane that lacks canonical porin proteins for the transport of small solutes to the periplasm. We discovered that 3,3-bis-di(methylsulfonyl)propionamide (3bMP1) inhibits the growth of M. tuberculosis, and resistance to this compound is conferred by mutation within a member of the proline-proline-glutamate (PPE) family, PPE51. ... Read more >>

Science (Science (New York, N.Y.))
[2020, 367(6482):1147-1151]

Cited: 20 times

View full text PDF listing >>



Synthesis, evaluation, molecular docking, and molecular dynamics studies of novel N-(4-[pyridin-2-yloxy]benzyl)arylamine derivatives as potential antitubercular agents.

Ruchi Verma, Helena I M Boshoff, Kriti Arora, Indira Bairy, Mradul Tiwari, Bhat G Varadaraj, G Gautham Shenoy,

A new series of novel triclosan (2,4,4'-trichloro-2'-hydroxydiphenylether) analogues were designed, synthesized, and screened for their in vitro antimycobacterial and antibacterial activities. Most of the compounds showed significant activity against Mycobacterium tuberculosis H37Rv strain with minimum inhibitory concentration (MIC) values in 20-40 μM range in GAST/Fe medium when compared with triclosan (43 μM) ... Read more >>

Drug Dev Res (Drug development research)
[2020, 81(3):315-328]

Cited: 1 time

View full text PDF listing >>



Dual-target inhibitors of mycobacterial aminoacyl-tRNA synthetases among N-benzylidene-N'-thiazol-2-yl-hydrazines.

Oksana P Kovalenko, Galyna P Volynets, Mariia Yu Rybak, Sergiy A Starosyla, Olga I Gudzera, Sergiy S Lukashov, Volodymyr G Bdzhola, Sergiy M Yarmoluk, Helena I Boshoff, Michael A Tukalo,

Effective treatment of tuberculosis is challenged by the rapid development of <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) multidrug resistance that presumably could be overcome with novel multi-target drugs. Aminoacyl-tRNA synthetases (AARSs) are an essential part of protein biosynthesis machinery and attractive targets for drug discovery. Here, we experimentally verify a hypothesis of simultaneous ... Read more >>

Medchemcomm (MedChemComm)
[2019, 10(12):2161-2169]

Cited: 1 time

View full text PDF listing >>



Targeting of Fumarate Hydratase from Mycobacterium tuberculosis Using Allosteric Inhibitors with a Dimeric-Binding Mode.

Andrew J Whitehouse, M Daben J Libardo, Monica Kasbekar, Paul D Brear, Gerhard Fischer, Craig J Thomas, Clifton E Barry, Helena I M Boshoff, Anthony G Coyne, Chris Abell,

With the growing worldwide prevalence of antibiotic-resistant strains of tuberculosis (TB), new targets are urgently required for the development of treatments with novel modes of action. Fumarate hydratase (fumarase), a vulnerable component of the citric acid cycle in <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>), is a metabolic target that could satisfy this unmet ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2019, 62(23):10586-10604]

Cited: 1 time

View full text PDF listing >>



C4-Phenylthio β-lactams: Effect of the chirality of the β-lactam ring on antimicrobial activity.

Rostislav Kuskovsky, Dina Lloyd, Kriti Arora, Balbina J Plotkin, Jacalyn M Green, Helena I Boshoff, Clifton Barry, Jeffrey Deschamps, Monika I Konaklieva,

C4-phenylthio β-lactams are a new family of antibacterial agents that have activity against two phylogenetically distant bacteria - Mycobacterium tuberculosis (Mtb) and Moraxella catarrhalis (M. cat). These compounds are effective against β-lactamase producing Mtb and M. cat unlike the clinically relevant β-lactam antibiotics. The structure-activity relationship for the C4 phenylthio ... Read more >>

Bioorg Med Chem (Bioorganic & medicinal chemistry)
[2019, 27(20):115050]

Cited: 1 time

View full text PDF listing >>



Design, synthesis, in silico and in vitro evaluation of novel diphenyl ether derivatives as potential antitubercular agents.

Ashutosh Prasad Tiwari, B Sridhar, Helena I Boshoff, Kriti Arora, G Gautham Shenoy, K E Vandana, G Varadaraj Bhat,

Diphenyl ether derivatives inhibit mycobacterial cell wall synthesis by inhibiting an enzyme, enoyl-acyl carrier protein reductase (InhA), which catalyses the last step in the fatty acid synthesis cycle of genus Mycobacterium. To select and validate a protein crystal structure of enoyl-acyl carrier protein reductase of Mycobacterium tuberculosis for designing inhibitors ... Read more >>

Mol Divers (Molecular diversity)
[2020, 24(4):1265-1279]

Cited: 0 times

View full text PDF listing >>



Mode-of-action profiling reveals glutamine synthetase as a collateral metabolic vulnerability of M. tuberculosis to bedaquiline.

Zhe Wang, Vijay Soni, Gwendolyn Marriner, Takushi Kaneko, Helena I M Boshoff, Clifton E Barry, Kyu Y Rhee,

Combination chemotherapy can increase treatment efficacy and suppress drug resistance. Knowledge of how to engineer rational, mechanism-based drug combinations, however, remains lacking. Although studies of drug activity have historically focused on the primary drug-target interaction, growing evidence has emphasized the importance of the subsequent consequences of this interaction. Bedaquiline (BDQ) ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2019, 116(39):19646-19651]

Cited: 10 times

View full text PDF listing >>



Construction of Fluorescent Analogs to Follow the Uptake and Distribution of Cobalamin (Vitamin B12) in Bacteria, Worms, and Plants.

Andrew D Lawrence, Emi Nemoto-Smith, Evelyne Deery, Joseph A Baker, Susanne Schroeder, David G Brown, Jennifer M A Tullet, Mark J Howard, Ian R Brown, Alison G Smith, Helena I Boshoff, Clifton E Barry, Martin J Warren,

Vitamin B<sub>12</sub> is made by only certain prokaryotes yet is required by a number of eukaryotes such as mammals, fish, birds, worms, and Protista, including algae. There is still much to learn about how this nutrient is trafficked across the domains of life. Herein, we describe ways to make a ... Read more >>

Cell Chem Biol (Cell chemical biology)
[2018, 25(8):941-951.e6]

Cited: 6 times

View full text PDF listing >>



Expanding Benzoxazole-Based Inosine 5'-Monophosphate Dehydrogenase (IMPDH) Inhibitor Structure-Activity As Potential Antituberculosis Agents.

Shibin Chacko, Helena I M Boshoff, Vinayak Singh, Davide M Ferraris, Deviprasad R Gollapalli, Minjia Zhang, Ann P Lawson, Michael J Pepi, Andrzej Joachimiak, Menico Rizzi, Valerie Mizrahi, Gregory D Cuny, Lizbeth Hedstrom,

New drugs and molecular targets are urgently needed to address the emergence and spread of drug-resistant tuberculosis. Mycobacterium tuberculosis ( Mtb) inosine 5'-monophosphate dehydrogenase 2 ( MtbIMPDH2) is a promising yet controversial potential target. The inhibition of MtbIMPDH2 blocks the biosynthesis of guanine nucleotides, but high concentrations of guanine can ... Read more >>

J Med Chem (Journal of medicinal chemistry)
[2018, 61(11):4739-4756]

Cited: 10 times

View full text PDF listing >>



Conformationally Constrained Cinnolinone Nucleoside Analogues as Siderophore Biosynthesis Inhibitors for Tuberculosis.

Surendra Dawadi, Helena I M Boshoff, Sae Woong Park, Dirk Schnappinger, Courtney C Aldrich,

5'-O-[N-(Salicyl)sulfamoyl]adenosine (Sal-AMS, 1) is a nucleoside antibiotic that inhibits incorporation of salicylate into siderophores required for bacterial iron acquisition and has potent activity against Mycobacterium tuberculosis (Mtb). Cinnolone analogues exemplified by 5 were designed to replace the acidic acyl-sulfamate functional group of 1 (pKa = 3) by a more stable ... Read more >>

ACS Med Chem Lett (ACS medicinal chemistry letters)
[2018, 9(4):386-391]

Cited: 7 times

View full text PDF listing >>



c-Oxidase-in-Mycobacterium-tuberculosis".">Correction for Arora et al., "Respiratory Flexibility in Response to Inhibition of Cytochrome c Oxidase in Mycobacterium tuberculosis".

Kriti Arora, Bernardo Ochoa-Montaño, Patricia S Tsang, Tom L Blundell, Stephanie S Dawes, Valerie Mizrahi, Tracy Bayliss, Claire J Mackenzie, Laura A T Cleghorn, Peter C Ray, Paul G Wyatt, Eugene Uh, Jinwoo Lee, Clifton E Barry, Helena I Boshoff,

Antimicrob Agents Chemother (Antimicrobial agents and chemotherapy)
[2017, 61(9):]

Cited: 0 times

c-Oxidase-in-Mycobacterium-tuberculosis".">View full text PDF listing >>



Advertisement


Disclaimer

1.0596 s