Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Articles

Vol. 1 No. 1 (2010): January-March 2010

Synthesis, In-vitro Evaluation and Computational Studies of Novel Isatinyl Derivatives for their Activity against HIV-TB Co-Infection

DOI
https://doi.org/10.37285/ijddd.1.1.8
Submitted
November 19, 2024
Published
2010-02-15

Abstract

The depleting T-lymphocyte count during acquired immunodeficiency syndrome (AIDS) predisposes the patients to many opportunistic infections, primary of which is Tuberculosis (TB). HIV-TB coinfection has acquired pandemic proportion especially in developing countries. Two series of novel N,N-diallyl/diphenyl-2-(5-substituted-1-(arylmethyl/alkylmethyl)-2-oxoindolin-3-ylidene)hydrazinecarbothioamide were synthesized and evaluated for their anti-retroviral capability on MT-4 cell lines as well as for their potential to repress TB in both logarithmic and dormant phases. They were also subjected to evaluation for their ability to repress Mycobacterium tuberculosis (MTB) Isocitrate lyase (ICL), an enzyme which is essential for the bacilli to survive in starved cultures. Amidst the entire array of compounds, N,N-diallyl-2-(1-((diethylamino)methyl)-5-methyl-2-oxoindolin-3-ylidene)hydrazinecarbothioamide (A12) demonstrated excellent activity against the growth of HIV-1 cell in vitro with EC50 value of 0.30 µM; and also had the best ICL inhibitory profile with 40.45% inhibition.

References

  1. 1. 2008 Report on the global AIDS epidemic. [Online]. 2008. Available from: URL: www.unaids.org
  2. 2. Global Tuberculosis Control. WHO Report 2008.[Online]. 2008. Available from: URL: http://www.who.int/tb/publications/global_report/2008/en /index.html
  3. 3. Idemyor, V. J Natl Med Assoc. 2007; 99, 1414.
  4. 4. Goletti, D.; Weissman, D.; Jackson, R.W.; Graham, N.M.; Vlahov, D.; Klein, R.S.; Munsiff, S.S.; Ortona, L.; Cauda, R.; Fauci, A.S. J. Immunol. 1996, 157, 1271.
  5. 5. Garrait, V.; Cadranel, J.; Esvant, H.; Herry, I.; Morinet, P.; Mayaud, C.; Israël-Biet, D. J. Immunol. 1997, 159, 2824.
  6. 6. Pepper, D. J.; Meintjes, G. A.; Mcllleron, H.; Wilkinson, R. J. Drug Discov. Today. 2007, 12, 980.
  7. 7. Narita, M.; Ashkin, D.; Hollender, E. S.; Pitchenik, A. E. Am. J. Respir. Crit. Care Med.1998, 158, 157.
  8. 8. Parrish, N. M.; Dick, J. D.; Bishai, W. R. Trends Microbiol. 1998, 6, 107.
  9. 9. Sharma, V.; Sharma, S.; Hoener zu Bentrup, K.; McKinney, J. D.; Russell, D. G.; Jacobs, W. R. Jr.; Sacchettini, J. C. Nat. Struct. Biol .2000, 7, 663.
  10. 10. Katz, E. Rev. Clin. Basic. Pharm. 1987, 6, 119.
  11. 11. Cooper, J. A.; Moss, B.; Katz, E. Virology. 1979, 96, 381.
  12. 12. Webber, S. E.; Tikhe, J.; Worland, S. T.; Fuhrman, S. A.; Hendrickson, T. F.; Matthews, D. A.; Love, R. A.; Patick,A. K.; Meador, J. W.; Ferre, R. A.; Brown, E. L.; DeLisle, D. M.; Ford, C. E.; Binford, S. L. J. Med. Chem. 1996, 39, 5072.
  13. 13. Ronen, D.; Sherman, L.; Bar-nun, S.; Teitz, Y. Antimicrob. Agents Chemother. 1987, 31, 1798.
  14. 14. Chen, L.R.; Wang, Y. C.; Lin, Y. W.; Chou, S. Y.; Chen, S. F.; Liu, L.T.; Wu, Y. T.; Kuo, C. J.; Chen, T. S.; Juang, S. H. Bioorg. Med. Chem. Lett. 2005, 15, 3058.
  15. 15. Teitz, Y.; Ronen, D.; Vansover, A.; Stematsky, T.; Riggs,J. L. Antiviral Res. 1994, 24, 305.
  16. 16. Bal, T. R.; Anand, B.; Yogeeswari, P.; Sriram, D. Bioorg. Med. Chem. Lett. 2005, 15, 4451.
  17. 17. Sriram, D.; Bal, T. R.; Yogeeswari, P. Bioorg. Med. Chem. 2004, 12, 5865.
  18. 18. National Committee for Clinical Laboratory Standards. Antimycobacterial susceptibility testing for Mycobacterium tuberculosis. Proposed standard M24-T. National Committee for Clinical Laboratory Standards, Villanova, PA, 1995.
  19. 19. Xie, Z.; Siddiqi, N.; Rubin, E. R. Antimicrob. Agents. Chemother. 2005, 49, 4778.
  20. 20. RCSB Protein Data Bank ID. 1VRT
  21. 21. RCSB Protein Data Bank ID. 1F8M
  22. 22. Jacobo-Molina, A.; Ding, J.; Nanni, R.G.; Clark, A.D. Jr.; Lu, X.; Tantillo, C.; Williams, R.L.; Kamer, G.; Ferris ,A. L.; Clark, P.; Hizi, A.; Hughes, S. H.; Arnold, E. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 6320.
  23. 23. Sarafianos, S.G.; Das, K.; Hughes, S.H.; Arnold, E. Curr. Opin. Struct. Biol. 2004, 14, 716.
  24. 24. Rodgers, D.W.; Gamblin, S.J.; Harris, B.A.; Ray, S.; Culp, J.S.; Hellmig, B.; Woolf, D.J.; Debouck, C.; Harrison, S.C. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 1222.
  25. 25. Rittinger, K.; Divita, G.; Goody, R.S. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 8046.
  26. 26. McKinney, J. D.; Höner zu Bentrup, K.; Muñoz-Elias, E. J.; Miczak, A.; Chen, B.; Chan, W. T.; Swenson, D.; Sacchettini, J. C.; Jacobs, W. R. Jr.; Russell, D. G. Nature. 2000, 46, 735.
  27. 27. Park, H.D. Mol. Microbiol. 2003, 48, 833.
  28. 28. Bentrup, K.H.Z.; Miczak, A.; Swenson, D.L.; Russell,D. G. J. Bacteriol. 1999, 181, 7161.

Similar Articles

<< < 1 2 

You may also start an advanced similarity search for this article.

Most read articles by the same author(s)