New Flexible Analogues of 8-Aza-7-deazapurine Nucleosides as Potential Antibacterial Agents.

A variety of ribo-, 2'-deoxyribo-, and 5'-norcarbocyclic derivatives of the 8-aza-7-deazahypoxanthine fleximer scaffolds were designed, synthesized, and screened for antibacterial activity. Both chemical and chemoenzymatic methods of synthesis for the 8-aza-7-deazainosine fleximers were compared. In the case of the 8-aza-7-deazahypoxanthine fleximer, the transglycosylation reaction proceeded with the formation of side products.

PLGA Carriers for Controlled Release of Levofloxacin in Anti-Tuberculosis Therapy.

Levofloxacin (LFX) is a highly effective anti-tuberculosis drug with a pronounced bactericidal activity against (). In this work, an "organic solvent-free" approach has been used for the development of polylactic-co-glycolic acid (PLGA) microparticles and scaffolds containing LFX at a therapeutically significant concentration, providing for its sustained release. To achieve the target, both nonpolar supercritical carbon dioxide and polar supercritical trifluoromethane have been used.

Evaluation of a new assay for nontuberculous mycobacteria species identification in diagnostic material and cultures.

The purpose of the present study was to evaluate a real-time PCR system for 12 nontuberculous mycobacteria (NTM) species identification developed by Central Tuberculosis Research Institute (CTRI; Moscow, Russia) in cooperation with Syntol LLC (Moscow, Russia). NTM cultures (210 strains, 19 species), Mycobacterium tuberculosis complex (MTBC) cultures (21 strains, 2 species), non-mycobacterial microorganisms (18 strains, 13 species) were used for the first stage of the assay evaluation. Clinical samples (sputum, N = 973) positive for smear microscopy and MTBC/NTM DNA by a PCR-based screening assay collected from 819 patients were used for specificity and sensitivity evaluation.

Interaction of 5-substituted pyrimidine nucleoside analogues and M.Tuberculosis: A view through an electron microscope.

The data of transmission electron microscopy (TEM) on morphology of M. tuberculosis H37Rv bacterial cells treated with four analogues of pyrimidine nucleosides with different substituents at 5 position of base are presented. We showed that the growth of M.

Investigation of 5'-Norcarbocyclic Nucleoside Analogues as Antiprotozoal and Antibacterial Agents.

Carbocyclic nucleosides have long played a role in antiviral, antiparasitic, and antibacterial therapies. Recent results from our laboratories from two structurally related scaffolds have shown promising activity against both and several parasitic strains. As a result, a small structure activity relationship study was designed to further probe their activity and potential.

New assay to diagnose and differentiate between Mycobacterium tuberculosis complex and nontuberculous mycobacteria.

The purpose of the present study was to create a real-time PCR test system allowing simultaneous detection of nontuberculous mycobacteria (NTM) and Mycobacterium tuberculosis complex (MTBC) both in culture and sputum. NTM cultures (18 strains, 18 species), MTBC cultures (16 strains, 2 species) and non-mycobacterial microorganisms from the collection of the Central Research TB Institute (CTRI) were used for the preliminary evaluation of the test system. 301 NTM cultures from patients with mycobacteriosis were used to assess the sensitivity of the developed test system.

Novel 5'-Norcarbocyclic Pyrimidine Derivatives as Antibacterial Agents.

A series of novel 5'-norcarbocyclic derivatives of 5-alkoxymethyl or 5-alkyltriazolyl-methyl uracil were synthesized and the activity of the compounds evaluated against both Gram-positive and Gram-negative bacteria. The growth of was completely inhibited by the most active compounds at a MIC of 67 μg/mL (mc²155) and a MIC of 6.7⁻67 μg/mL (VKPM Ac 1339).

Dual-targeted anti-TB/anti-HIV heterodimers.

HIV and M. tuberculosis are two intersecting epidemics making the search for new dual action drugs against both pathogens extremely important. Here, we report on the synthesis and suppressive activities of five dual-targeted HIV/TB compounds.

Mycobacterium tuberculosis Type II Toxin-Antitoxin Systems: Genetic Polymorphisms and Functional Properties and the Possibility of Their Use for Genotyping.

Various genetic markers such as IS-elements, DR-elements, variable number tandem repeats (VNTR), single nucleotide polymorphisms (SNPs) in housekeeping genes and other groups of genes are being used for genotyping. We propose a different approach. We suggest the type II toxin-antitoxin (TA) systems, which play a significant role in the formation of pathogenicity, tolerance and persistence phenotypes, and thus in the survival of Mycobacterium tuberculosis in the host organism at various developmental stages (colonization, infection of macrophages, etc.

Resistance to pyrazinamide in Russian Mycobacterium tuberculosis isolates: pncA sequencing versus Bactec MGIT 960.

Resistance to pyrazinamide (PZA) may impact clinical outcome of anti-tuberculosis chemotherapy. PZA susceptibility testing using MGIT 960 is not reliable and little information is available on the prevalence of PZA resistance in Russia. A collection of 64 clinical isolates of Mycobacterium tuberculosis, including 35 multidrug resistant and extensively drug-resistant (MDR/XDR), was analyzed for PZA resistance using MGIT 960, Wayne test, and sequencing of PZA resistance genes pncA, rpsA and panD.