Tuberculostatic Activity of 2-Amino-6-Chloropurine Derivatives.

Krasnov, V.; Vigorov, A.; Gruzdev, D.; Levit, G.; Kravchenko, M.; Skornyakov, S.; Bekker, O.; Maslov, D.; Danilenko, V.; Charushin, V.

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 (IC > 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.

ANTITUBERCULAR agents; AMINO acid amides; TUBERCULOSIS; LUNG diseases; SERINE

Pharmaceutical Chemistry Journal, 2017, Vol 51, Issue 9, p769

0091-150X

Academic Journal

10.1007/s11094-017-1690-4