Studies of the antimycobacterial activity of 2-amino-6-chloropurine and its N-acyl derivatives against laboratory (Mycobacterium tuberculosis H37Rv, M. avium, M. terrae) and clinical Mycobacterium tuberculosis strains (MDR-TB) identified compounds with high tuberculostatic activity (MIC from 0.35 – 1.5 μg/ml). The cytotoxic activities of the compounds with antimycobacterial activity against human embryo fibroblasts were studied in the MTT test, which showed that the study compounds were essentially nontoxic (IC50 > 50 μM). Further chemical modification may yield compounds with potential for creating drugs for the treatment of tuberculosis. With the aim of identifying the possible mechanism of the tuberculostatic activity, the ability of the study compounds to inhibit mycobacterial serine-threonine protein kinases (STPK) was assessed. The tuberculostatic activity of 2-amino-6-chloropurine derivatives was not linked with their inhibition of STPK.
Similar content being viewed by others
References
V. Bhowruth, L. G. Dover, and G. S. Besra, Prog. Med. Chem., 45, 169 – 203 (2007).
WHO Global Tuberculosis Report (2015). URL: http: //apps.who.int / iris / bitstream / 10665 / 191102 / 1 /9789241565059 eng.pdf.
L. G. Dover and G. D. Coxon, J. Med. Chem., 54, 6157 – 6165 (2011).
B. Rawat and D. S. Rawat, Med. Res. Rev., 33, 693 – 764 (2013).
A. Scozzafava, A. Mastrolorenzo, and C. T. Supuran, Bioorg. Med. Chem. Lett., 11, 1675 – 1678 (2001).
M. Brzhndvang, V. Bakken, and L.-L. Gundersen, Bioorg. Med. Chem., 17, 6512 – 6516 (2009).
A. K. Pathak, V. Pathak, L. E. Seitz, et al., Bioorg. Med. Chem., 21, 1685 – 1695 (2013).
A. K. Bakkestuen, L.-L. Gundersen, D. Petersen, et al., Org. Biomol. Chem., 3, 1025 – 1033 (2005).
A. Vik, E. Hedner, C. Charnock, L. W. Tangen, et al., Bioorg. Med. Chem., 15, 4016 – 4037 (2007).
C. Correia, M. A. Carvalho, and M. F. Proenza, Tetrahedron, 65, 6903 – 6911 (2009).
Y. L. Hu, X. Liu, M. Lu, et al., J. Korean Chem. Soc., 54(4), 429 – 436 (2010).
A. B. Bowles, F. H. Schneider, L. R. Lewis, and R. K. Robins, J. Med. Chem., 6, 471 – 480 (1963).
L.-H. Huang, H.-D. Xu, Z.-Y. Yao, et al., Bioorg. Med. Chem. Lett., 24, 973 – 975 (2014).
L.-L. Gundersen, J. Nissen-Meyer, and B. Spilsber, J. Med. Chem., 45, 1383 – 1386 (2002).
M. Knockaert, N. Gray, E. Damiens, et al., Chem. Biol. (Oxford, UK), 7, 411 – 422 (2000).
L. Meijer and E. Raymond, Acc. Chem. Res., 36, 417 – 425 (2003).
M. Legraverend and D. S. Grierson, Bioorg. Med. Chem., 14, 3987 – 4006 (2006).
M. Yu. Steklov, V. I. Tararov, G. A. Romanov, and S. N. Mikhailov, Nucleosides, Nucleotides Nucleic Acids, 30, 503 – 511 (2011).
A. Yu. Vigorov, V. P. Krasnov, D. A. Gruzdev, et al., Mendeleev Commun., 24, 35 – 36 (2014).
S. Fletcher, V. M. Shahani, A. J. Lough, and P. T. Gunning, Tetrahedron, 66, 4621 – 4632 (2010).
S. Kudon and T. Kudon, “Study on the isolation culture technique of tubercle bacilli applicable in remote areas, part 1”, Kekkaku (Tuberculosis), 48(10), 453 – 462 (1973).
T. Mosmann, J. Immunol. Methods, 65, 55 – 63 (1983).
O. B. Bekker, D. N. Sokolov, O. A. Luzina, et al., Med. Chem. Res., 24, 2926 – 2938 (2015).
S. M. Elizarov, O. V. Sergienko, I. A. Sizova, V. N. Danilenko, Molek. Biol., 39(2), 1 – 9 (2005).
G. G. Mordovskoi, USSR patent No. 278039 (1970); Byul. Izobret., No. 25 (1970).
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 51, No. 9, pp. 20 – 23, September, 2017.
Rights and permissions
About this article
Cite this article
Krasnov, V.P., Vigorov, A.Y., Gruzdev, D.A. et al. Tuberculostatic Activity of 2-Amino-6-Chloropurine Derivatives. Pharm Chem J 51, 769–772 (2017). https://doi.org/10.1007/s11094-017-1690-4
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11094-017-1690-4