Antinociceptive and Antimicrobial Activity of Products from Reactions of Pyrrolobenzoxazinetriones with Thiosemicarbazones of Aromatic and Heteroaromatic Aldehydes

Previously, a series of hetareno[e]pyrrole-2,3-diones was found to include compounds with high antimicrobial and antinociceptive activity and low toxicity, so that new hetareno[e]pyrrole-2,3-dione derivatives were expected to have these types of activity. The reactions of pyrrolobenzoxazinetriones with a series of aromatic aldehyde thiosemicarbazones and nicotinic aldehyde thiosemicarbazone are reported. Results from studies of the antinociceptive (hot-plate test) and antimicrobial activity (Staphylococcus aureus No. 906, Escherichia coli No. 1257) are given. The most active compounds were effective on the level of the reference drugs. The target of the antinociceptive activity of the tested compounds was considered nerve endings because signs of central action were not observed in the behavior of animals under the influence of the compounds. The selective antimicrobial activity against Gram-positive bacteria S. aureus was presumably associated with disruption of the cytoplasmic membrane permeability and bacterial RNA synthesis.

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References

  1. 1.

    I. V. Mashevskaya, R. R. Makhmudov, G. A. Aleksandrova, et al., Khim.-farm. Zh., 35(4), 20 – 21 (2001).

    Google Scholar 

  2. 2.

    I. V. Mashevskaya, R. R. Makhmudov, G. A. Aleksandrova, et al., Khim.-farm. Zh., 34(12), 13 – 16 (2000).

    Google Scholar 

  3. 3.

    I. V. Mashevskaya, L. V. Anikina, Yu. B. Vikharev, et al., RU Pat. No. 2,199,537, Feb. 27, 2003.

  4. 4.

    I. V. Mashevskaya, R. R. Makhmudov, G. A. Aleksandrova, et al., Khim.-farm. Zh., 35(2), 11 – 12 (2001).

    Google Scholar 

  5. 5.

    E. J. Blanz and F. A. French, Cancer Res., 28, 2419 – 2422 (1968).

    CAS  PubMed  Google Scholar 

  6. 6.

    Y. Wang, M. C. Liu, T. S. Lin, et al., J. Med. Chem., 35, 3667 – 3671 (1992).

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    D. Sriram, P. Yogeeswari, R. Thirumurugan, et al., J. Med. Chem., 49(12), 3448 – 3450 (2006).

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    M. C. Pirrung, S. V. Pansare, K. D. Sarma, et al., J. Med. Chem., 48(8), 3045 – 3050 (2005).

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    J. S. Casas, E. E. Castellano, A. Macias, et al., J. Chem. Soc., Dalton Trans., No. 2, 353 – 354 (1933); doi: 10.1039/DT9930000353.

  10. 10.

    C.-S. Niu, J. Li, K. Li, et al., RU Pat. No. 2,198,875, Feb. 20, 2003.

  11. 11.

    D. N. Lukmanova, Ya. I. Prikhod’ko, M. V. Dmitriev, I. V. Mashevskaya, and A. N. Maslivets, Zh. Org. Khim., 55(1), 149 – 156 (2019).

    Article  Google Scholar 

  12. 12.

    A. N. Maslivets, I. V. Mashevskaya, L. I. Smirnova, et al., Zh. Org. Khim., 28(12), 2545 – 2547 (1992).

    Google Scholar 

  13. 13.

    N. B. Eddy and D. J. Leimbach, J. Pharmacol. Exp. Ther., 107(3), 385 – 393 (1953).

    CAS  PubMed  Google Scholar 

  14. 14.

    A. N. Mironov (ed.), Handbook for Preclinical Drug Trials [in Russian], Grif i K, Moscow (2012).

  15. 15.

    V. E. Kolla and B. Ya. Syropyatov, Doses of Drugs and Chemical Compounds for Laboratory Animals [in Russian], Meditsina, Moscow (1998), p. 14.

    Google Scholar 

  16. 16.

    Ya. A. Sigidin, G. Ya. Shvarts, A. P. Arzamastsev, and S. S. Liberman, Drug Therapy of the Inflammatory Process: Experimental and Clinical Pharmacology of Anti-inflammatory Drugs [in Russian], Meditsina, Moscow (1988).

    Google Scholar 

  17. 17.

    M. L. Belen’kii, Elements of Quantitative Assessment of a Pharmacological Effect [in Russian], Leningrad (1963), pp. 81 – 106.

  18. 18.

    N. F. Izmerov, I. V. Sanotskii, and K. K. Sidorov, Toxicometry Parameters of Industrial Poisons with a Single Exposure [in Russian], Meditsina, Moscow (1977), pp. 196 – 197.

    Google Scholar 

  19. 19.

    G. N. Pershin, Methods of Experimental Chemotherapy [in Russian], Meditsina, Moscow (1971), p. 109.

    Google Scholar 

Download references

Acknowledgments

The studies were financially supported by the Administration of Perm Krai under Science Project No. C-26/174.5 and in the framework of the Perm Krai Program for Science School Development “Biologically Active Heterocycles (Department of Organic Chemistry, PSNRU).”

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Correspondence to I. V. Mashevskaya.

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Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 54, No. 3, pp. 37 – 31, March, 2020.

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Lukmanova, D.N., Balandina, S.Y., Makhmudov, R.R. et al. Antinociceptive and Antimicrobial Activity of Products from Reactions of Pyrrolobenzoxazinetriones with Thiosemicarbazones of Aromatic and Heteroaromatic Aldehydes. Pharm Chem J 54, 236–240 (2020). https://doi.org/10.1007/s11094-020-02186-y

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Keywords

  • pyrrolobenzoxazinetriones
  • thiosemicarbazones
  • antinociceptive and antimicrobial activity