Synthesis and biological evaluation of some bicyclic [2-(2,4-dimethylphenylthio)phenyl] aniline and its amide derivatives as potential antitubercular agents

  • Yogesh Patil
  • Ramesh Shingare
  • Shakti Chakraborty
  • Rachana Borkute
  • Dhiman Sarkar
  • Balaji Madje
Regular Article
  • 24 Downloads

Abstract

In the present investigation, a series of bicyclic [2-(2,4-dimethylphenylthio)phenyl] aniline analogues were synthesized and characterized by IR, NMR (\(^{1}\)H and \(^{13}\)C) and mass spectra. All newly synthesized 15 compounds were inspected for their in vitro antitubercular activity against Mycobacterium tuberculosis (MTB) \(\hbox {H}_{37}\)Ra in both active and dormant state using an established XTT Reduction Menadione assay (XRMA). The titled compounds exhibited minimum inhibitory concentration (MIC90) ranging from 0.05 to >30 (\(\upmu \)g/mL). The potent four compounds were further evaluated in THP-1 infection model where they demonstrated significant antitubercular activity. All the ex vivo active were further evaluated for cytotoxic activity against THP-1, MCK-7 and HeLa cell lines in order to check selectivity index. All compounds were further screened against four different bacteria to assess their selectivity towards MTB. These derivatives could be considered as a precursor structure for further design of antituberculosis agent.

Graphical Abstract

SYNOPSIS A series of bicyclic [2-(2,4-dimethylphenylthio)phenyl] aniline analogues were synthesized. All newly synthesized 15 compounds were inspected for their in vitro antitubercular activity against Mycobacterium tuberculosis (MTB) \(\hbox {H}_{37}\)Ra in both active and dormant state using an established XTT Reduction Menadione assay (XRMA).

Keywords

[2-(2,4-dimethylphenylthio)phenyl] aniline antituberculosis activity cytotoxicity 

Notes

Acknowledgements

Authors are thankful to the Department of Science & Technology, New Delhi, India for financial support under Fast Track Young Scientist Schemes and are grateful to the Principal and Head, Department of Chemistry for providing research facilities.

Supplementary material

12039_2018_1424_MOESM1_ESM.pdf (994 kb)
Supplementary material 1 (pdf 994 KB)

References

  1. 1.
    The World Health Organization (WHO) 2014 Global Tuberculosis Report  https://doi.org/10.1016/S2214109X(14)70361-4 (accessed on January 2015)
  2. 2.
    Abubakar I, Zignol M, Falzon D, Raviglione M, Ditiu L, Masham S, Adetifa I, Ford N, Cox H and Lawn S D 2013 Drug-resistant tuberculosis: time for visionary political leadership Lancet Infect. Dis. 13 529CrossRefGoogle Scholar
  3. 3.
    The World Health Organization (WHO) 2015 Global Tuberculosis Report http://www.who.int/tb/publications/global_report/en/ (accessed on November 2015)
  4. 4.
    Espinal M A 2003 The global situation of MDR-TB Tuberculosis 83 44CrossRefGoogle Scholar
  5. 5.
    Jones T R, Webber S E, Varney M D, Reddy M R, Lewis K K, Kathardekar V, Mazdiyasni H, Deal J, Nguyen D, Welsh K M, Webber S, Johnston A, Matthews D A, Smith W W, Janson C A, Bacquet R J, Hwland E F, Booth C L J, Herrmann S M, Ward R W, White J, Bartlett C A and Morse C A 1997 Structure-based design of substituted diphenyl sulfones and sulfoxides as lipophilic inhibitors of thymidylate synthase J. Med. Chem. 40 677CrossRefGoogle Scholar
  6. 6.
    Sreekanth A, Ramachandran P S, Jadhavar S K, Miglani M P, Singh D P, Kalane A K, Agarwal B D, Sathe K M, Gupta A, Haldar S, Mohd R, Singh S, Pham S M, Chakravarty S, Kevin Q, Sebastian B, Ivan E A, Higgs C, Francisco J and Herrera R 2017 Design, synthesis and optimization of bis-amide derivatives as CSF1R inhibitors Bioorg. Med. Chem. Lett. 27 2153CrossRefGoogle Scholar
  7. 7.
    Caroline R, Montes T C, Tamara G M, Carolina R L, Hack R D, Pedro A S, Marcelo G and Montes D 2010 Synthesis and antituberculosis activity of new fatty acid amides Bioorg. Med. Chem. Lett. 20 5255CrossRefGoogle Scholar
  8. 8.
    Yang Z B, Hu D Y, Zeng S and Bao A S 2016 Novel hydrazone derivatives containing pyridine amide moiety: Design, synthesis, and insecticidal activity Bioorg. Med. Chem. Lett. 26 1161CrossRefGoogle Scholar
  9. 9.
    Yamaki S, Suzuki D, Fujiyasu J, Neya M, Nagashima A, Kondo M, Takafumi A, Keitaro K, Ayako M and Yoshihara Y 2017 Synthesis and pharmacological evaluation of glycine amide derivatives as novel vascular adhesion protein-1 inhibitors without CYP3A4 and CYP2C19 inhibition Bioorg. Med. Chem. 25 4110CrossRefGoogle Scholar
  10. 10.
    Francisco G A A, Eugenio H F, Pilar C R, Susana L C, Jorge H F, Mario O, Nancy E G D, Alejandro M V, Víctor M V M and Maria G S M 2017 Synthesis, antimycobacterial and cytotoxic activity of \(\upalpha \), \(\upbeta \)-unsaturated amides and 2, 4-disubstituted oxazoline derivatives Bioorg. Med. Chem. Lett. 27 821CrossRefGoogle Scholar
  11. 11.
    Yang K, Guo S S, Geng Z F, You C X, Zhang W J, Li Y P, Wang C F, Du S S and Deng Z W 2015 Five new sulphur-containing amides from Glyco smislucida with antifeedant activity against Tribolium castaneum Ind. Crops Prod. 74 628CrossRefGoogle Scholar
  12. 12.
    Greger H and Zechner G 1996 Bioactive Amides from Glycosmis species J. Nat. Prod. 59 1163CrossRefGoogle Scholar
  13. 13.
    Tarbell D S and Fukushima D K 1947 M-Thiocresol Org. Synth. 27 81CrossRefGoogle Scholar
  14. 14.
    Leuckart R J 1890 Eine neue Methode zur Darstellung aromatischer Mercaptane J. Prakt. Chem. 41 179CrossRefGoogle Scholar
  15. 15.
    Molly S H, Alice L P and Atli T 1999 Palladium catalyzed bispyrimidine thioether synthesis Synlett 10 1579Google Scholar
  16. 16.
    Mao Y, Jiang L, Chen T, He H, Liu G and Wang H 2015 A new and practical synthesis of Vortioxetine Hydrobromide Synthesis 47 1387CrossRefGoogle Scholar
  17. 17.
    Qunfeng Z, Wei X, Xiaonian Li, Dahao J, Yizhi X, Jianguo W, Jie C, Stephen R and Jun N 2015. Catalytic hydrogenation of sulfur-containing nitrobenzene over Pd/C catalysts: In situ sulfidation of Pd/C for the preparation of \({\rm Pd}_{x}{\rm S}_{y}\) catalysts Appl. Catal. A Gen. 497 17CrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2018

Authors and Affiliations

  • Yogesh Patil
    • 1
  • Ramesh Shingare
    • 1
  • Shakti Chakraborty
    • 2
  • Rachana Borkute
    • 2
  • Dhiman Sarkar
    • 2
  • Balaji Madje
    • 1
  1. 1.Department of ChemistryVasantrao Naik MahavidhyalayaAurangabadIndia
  2. 2.Combi Chem Bio Resource CentreNational Chemical LaboratoryPuneIndia

Personalised recommendations