Serghei Pogrebnoi

The structure–antituberculosis activity relationships study in a series of 5-aryl-2-thio-1,3,4-oxadiazole derivatives

A series of 82 5-aryl-2-thio-1,3,4-oxadiazole derivatives were screened for their anti-mycobacterial activities against Mycobacterium tuberculosis H37Rv. The synthesized compounds 30-37 appeared to be the most active derivatives exhibiting more than 90% inhibition of mycobacterial growth at 12.5 μg/mL. Structure-activity relationships study was performed for the given series by using the electronic-topological method combined with neural networks (ETM-NN). A system for the anti-mycobacterial activity prediction was developed as the result of training associative neural network (ASNN) with weights calculated from projections of a compound and each pharmacophoric fragment found on the elements of the Kohonens self-organizing maps (SOMs). From the detailed analysis of all compounds under study, the necessary requirements for a compound to possess antituberculosis activity have been formulated. The analysis has shown that any requirements violation for a molecule implies a considerable decrease or even complete loss of its activity. Molecular docking studies of the compounds allowed shedding light on the binding mode of these novel anti-mycobacterial inhibitors.

Chalcone Scaffold based Antimycobacterial Agents

This article represents a mini-review dedicated to chalcone derivatives with antimycobacterial activity. Natural and synthetic chlacones are reviewed. General and specific schemes of synthesis of chalchone derivatives are presented. QSAR and docking studies of certain chalcones are analyzed in respect of their antimycobacterial activity and inhibition of Mycobacterium tuberculosis enzymes.

Preparation of alginate–chitosan–cyclodextrin micro- and nanoparticles loaded with anti-tuberculosis compounds

Summary This paper describes the synthesis and application of alginate–chitosan–cyclodextrin micro- and nanoparticulate systems loaded with isoniazid (INH) and isoconazole nitrate (ISN) as antimycobacterial compounds. Preparation and morphology of the obtained particles, as well as antimycobacterial activity data of the obtained systems are presented. Docking of isoconazole into the active site of enoyl–acyl carrier protein reductase (InhA) of Mycobacetrium tuberculosis was carried out in order to predict the binding affinity and non-covalent interactions stabilizing the InhA–isoconazole complex. To assess these interactions, frontier molecular orbital calculations were performed for the active site of InhA and isoconazole obtained from docking. Isoconazole was predicted to be an active inhibitor of InhA with the analysis of the molecular docking and electron density distribution. It has been detected that alginate–chitosan–cyclodextrin microparticulate systems loaded with INH and ISN are as effective as pure INH applied in higher dosages.

Initial Synthesis of Diastereomeric Pyran Spirooxoindolinones Based on (–)-Carvone and (+)-3-Carene

Diastereomeric 2′-amino-3′-cyano-6′-methyl-2-oxospiro[indolin-3,4′-pyran]-5′-carboxylates based on transformation products of (+)-3-carene and (–)-carvone were synthesized for the first time.