Туберкулостатическая активность производных 2-амино-6-хлорпурина

As a result of studying the antimycobacterial activity of 2-amino-6-chloropurine and its N-acyl derivatives against laboratory strains ( Mycobacterium tuberculosis H37Rv, M. avium , M. terrae ) and clinical isolates of multidrug-resistant M. tuberculosis (MDR-TB) strains, compounds exhibiting high tuberculostatic activity (MIC from 0.35 to 1.5 mg/mL) were identified and the cytotoxic activity of selected compounds against human embryonic fibroblasts was studied in MTT assay. It has been found that these compounds are practically nontoxic (IC 50 50 μM). Their further chemical modification can lead to compounds that are promising for designing drugs for tuberculosis treatment. In order to elucidate the possible mechanism of tuberculostatic activity, the ability of compounds to inhibit mycobacterial serine-threonine protein kinases (Ser/Thr PKs) was studied. It is established that the tuberculostatic activity of 2-amino-6-chloropurine derivatives is not associated with the inhibition of Ser/Thr PKs.