Literature DB >> 26257441

Evolution of a thienopyrimidine antitubercular relying on medicinal chemistry and metabolomics insights.

Shao-Gang Li1, Catherine Vilchèze2, Sumit Chakraborty3, Xin Wang1, Hiyun Kim1, Monica Anisetti1, Sean Ekins4, Kyu Y Rhee3, William R Jacobs2, Joel S Freundlich5.   

Abstract

The metabolic instability of an antitubercular small molecule CD117 was addressed through iterative alteration of a key sulfide substituent and interrogation of the effect on growth inhibition of cultured Mycobacterium tuberculosis. This process was informed by studies of the intramycobacterial metabolism of CD117 and its inactive carboxylic acid derivative. Isoxazole 4e and thiazole 4m demonstrated significant gains in mouse liver microsomal stability with slight losses in whole-cell activity. This work illustrates the challenges of antitubercular hit evolution, requiring a balance of chemical and biological insights.

Entities:  

Keywords:  metabolomics; prodrug; thienopyrimidine; tuberculosis

Year:  2015        PMID： 26257441      PMCID： PMC4527344          DOI： 10.1016/j.tetlet.2015.02.129

Source DB:  PubMed          Journal:  Tetrahedron Lett        ISSN： 0040-4039            Impact factor:   2.415


  28 in total

Review 1.  Drugs versus bugs: in pursuit of the persistent predator Mycobacterium tuberculosis.

Authors:  James C Sacchettini; Eric J Rubin; Joel S Freundlich
Journal:  Nat Rev Microbiol       Date:  2008-01       Impact factor: 60.633

2.  Population genetics study of isoniazid resistance mutations and evolution of multidrug-resistant Mycobacterium tuberculosis.

Authors:  Manzour Hernando Hazbón; Michael Brimacombe; Miriam Bobadilla del Valle; Magali Cavatore; Marta Inírida Guerrero; Mandira Varma-Basil; Helen Billman-Jacobe; Caroline Lavender; Janet Fyfe; Lourdes García-García; Clara Inés León; Mridula Bose; Fernando Chaves; Megan Murray; Kathleen D Eisenach; José Sifuentes-Osornio; M Donald Cave; Alfredo Ponce de León; David Alland
Journal:  Antimicrob Agents Chemother       Date:  2006-08       Impact factor: 5.191

Review 3.  How sisters grow apart: mycobacterial growth and division.

Authors:  Karen J Kieser; Eric J Rubin
Journal:  Nat Rev Microbiol       Date:  2014-07-07       Impact factor: 60.633

4.  Novel inhibitors of InhA efficiently kill Mycobacterium tuberculosis under aerobic and anaerobic conditions.

Authors:  Catherine Vilchèze; Anthony D Baughn; JoAnn Tufariello; Lawrence W Leung; Mack Kuo; Christopher F Basler; David Alland; James C Sacchettini; Joel S Freundlich; William R Jacobs
Journal:  Antimicrob Agents Chemother       Date:  2011-05-31       Impact factor: 5.191

5.  Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis.

Authors:  O Zimhony; J S Cox; J T Welch; C Vilchèze; W R Jacobs
Journal:  Nat Med       Date:  2000-09       Impact factor: 53.440

Review 6.  Global control of tuberculosis: from extensively drug-resistant to untreatable tuberculosis.

Authors:  Keertan Dheda; Tawanda Gumbo; Neel R Gandhi; Megan Murray; Grant Theron; Zarir Udwadia; G B Migliori; Robin Warren
Journal:  Lancet Respir Med       Date:  2014-03-24       Impact factor: 30.700

7.  High affinity InhA inhibitors with activity against drug-resistant strains of Mycobacterium tuberculosis.

Authors:  Todd J Sullivan; James J Truglio; Melissa E Boyne; Polina Novichenok; Xujie Zhang; Christopher F Stratton; Huei-Jiun Li; Tejinder Kaur; Amol Amin; Francis Johnson; Richard A Slayden; Caroline Kisker; Peter J Tonge
Journal:  ACS Chem Biol       Date:  2006-02-17       Impact factor: 5.100

8.  Targeting tuberculosis and malaria through inhibition of Enoyl reductase: compound activity and structural data.

Authors:  Mack R Kuo; Hector R Morbidoni; David Alland; Scott F Sneddon; Brian B Gourlie; Mark M Staveski; Marina Leonard; Jill S Gregory; Andrew D Janjigian; Christopher Yee; James M Musser; Barry Kreiswirth; Hiroyuki Iwamoto; Remo Perozzo; William R Jacobs; James C Sacchettini; David A Fidock
Journal:  J Biol Chem       Date:  2003-02-26       Impact factor: 5.157

9.  Analogs of a 4-aminothieno[2,3-d]pyrimidine lead (QB13) as modulators of P-glycoprotein substrate specificity.

Authors:  Hans-Georg Häcker; Antje de la Haye; Katja Sterz; Gregor Schnakenburg; Michael Wiese; Michael Gütschow
Journal:  Bioorg Med Chem Lett       Date:  2009-09-11       Impact factor: 2.823

Review 10.  The mechanism of isoniazid killing: clarity through the scope of genetics.

Authors:  Catherine Vilchèze; William R Jacobs
Journal:  Annu Rev Microbiol       Date:  2007       Impact factor: 15.500
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  5 in total

1.  Addressing the Metabolic Stability of Antituberculars through Machine Learning.

Authors:  Thomas P Stratton; Alexander L Perryman; Catherine Vilchèze; Riccardo Russo; Shao-Gang Li; Jimmy S Patel; Eric Singleton; Sean Ekins; Nancy Connell; William R Jacobs; Joel S Freundlich
Journal:  ACS Med Chem Lett       Date:  2017-09-14       Impact factor: 4.345

2.  Novel Pyrimidines as Antitubercular Agents.

Authors:  Daigo Inoyama; Steven D Paget; Riccardo Russo; Srinivasan Kandasamy; Pradeep Kumar; Eric Singleton; James Occi; Margareta Tuckman; Matthew D Zimmerman; Hsin Pin Ho; Alexander L Perryman; Véronique Dartois; Nancy Connell; Joel S Freundlich
Journal:  Antimicrob Agents Chemother       Date:  2018-02-23       Impact factor: 5.191

3.  Combining Metabolite-Based Pharmacophores with Bayesian Machine Learning Models for Mycobacterium tuberculosis Drug Discovery.

Authors:  Sean Ekins; Peter B Madrid; Malabika Sarker; Shao-Gang Li; Nisha Mittal; Pradeep Kumar; Xin Wang; Thomas P Stratton; Matthew Zimmerman; Carolyn Talcott; Pauline Bourbon; Mike Travers; Maneesh Yadav; Joel S Freundlich
Journal:  PLoS One       Date:  2015-10-30       Impact factor: 3.240

Review 4.  Antimycobacterial Metabolism: Illuminating Mycobacterium tuberculosis Biology and Drug Discovery.

Authors:  Divya Awasthi; Joel S Freundlich
Journal:  Trends Microbiol       Date:  2017-06-13       Impact factor: 17.079

5.  Design, synthesis, crystal structure and anti-plasmodial evaluation of tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives.

Authors:  Kavita Pal; Md Kausar Raza; Jenny Legac; Md Ataur Rahman; Shoaib Manzoor; Philip J Rosenthal; Nasimul Hoda
Journal:  RSC Med Chem       Date:  2021-05-18
  5 in total

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