Veaceslav Boldescu

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.

Cyclodextrins in Asymmetric and Stereospecific Synthesis

Since their discovery, cyclodextrins have widely been used as green and easily available alternatives to promoters or catalysts of different chemical reactions in water. This review covers the research and application of cyclodextrins and their derivatives in asymmetric and stereospecific syntheses, with their division into three main groups: (1) cyclodextrins promoting asymmetric and stereospecific catalysis in water; (2) cyclodextrins’ complexes with transition metals as asymmetric and stereospecific catalysts; and (3) cyclodextrins’ non-metallic derivatives as asymmetric and stereospecific catalysts. The scope of this review is to systematize existing information on the contribution of cyclodextrins to asymmetric and stereospecific synthesis and, thus, to facilitate further development in this direction.

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.

Recent advances in the use of cyclodextrins in antifungal formulations.

Cyclodextrins are usually used in antifungal formulations as auxiliary substances to improve solubility, stability, or other physicochemical properties of the active compound. Nevertheless, more and more research and practical use results indicate that cyclodextrins might also act as active compounds in pharmaceutical formulations. The biological effects of cyclodextrins, important for their use within antimycotic formulations, can be divided into: effects based on the ability of cyclodextrins to form inclusion complexes with endogenous substances (membrane lipids, cellular cholesterol), effects based on formation of inclusion complexes with component parts of fungi cells, and effects based on the chemical nature of cyclodextrins and their derivatives. This review will cover the advances in research of biological activity of cyclodextrins with focus on their properties responsible for their synergistic effect with antimycotic compounds.

PHARMACEUTICALS AND PERSONAL CARE PRODUCTS IN THE ENVIRONMENT

Various problems concerning the pharmaceutical and personal care products (PPCPs) in the environment of the Eastern European countries are described. The main classes of PPCPs in the environment, as well as major occurrence pathways and PPCPs fate, are depicted. The influence of specifics of the regional pharmaceutical market, medication consumption culture and pharmaceutical waste disposal techniques on environmental pollution with PPCPs, are discussed. Examples of wrong drugs prescription, drugs misuse, drugs overconsumption, and poor pharmaceutical waste management are presented. The necessity in research and management of PPCPs with emphasize on the local specifics and practices are concluded.

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.

Ectonucleotidase Inhibitory and Redox Activity of Imidazole‐Based Organic Salts and Ionic Liquids

Cytotoxicity against cancer and normal cells, inhibition of ectonucleotidase, and redox properties of a new group of imidazole‐based organic salts and ionic liquids were studied. The tetrachloroferrate salt of a 1‐methylimidazole derivative of salicylic aldehyde had most prominent inhibitory activity against ectonucleotidase as well as a higher cytotoxicity against HeLa cells and lower cytotoxicity against BHK‐21 cells than the reference compound carboplatin. The studied compounds exhibited a moderate level of antioxidant activity with better results for the salicylic aldehyde derivatives than for spiropyrans. Moreover, these compounds did not generate singlet oxygen.