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Symmetric and asymmetric derivatives of (–)-convolutamydine and analogs in which 3-hydroxy-2-oxindole fragments were conjugated through a 2-oxopropyl linker were synthesized. Monobromoxindole 10 from the reaction of (S)-3-hydroxy-3-(2-oxopropyl)indolin-2-one and 5-bromoisatin exhibited the greatest cytotoxicity of all tested compounds with CC50 = 0.197 mM in acutely infected MT-4 cells. The cytotoxicities of dibromo derivatives 7 and 9 decreased as compared to 10 to CC50 = 0.205 and 0.245 mM, respectively.

Mental illnesses are a current public health problem, as their incidence and prevalence are constantly increasing. Depressive disorders are some of the most common psychiatric disorders. According to WHO data, the number of people suffering from depression has increased by 18 percent over the last decade, globally, reaching 322 million. Mental disorder therapy requires continuous updating. In the Laboratory of Organic synthesis and biopharmaceuticals of the Institute of Chemistry was synthesized a new compound, derivative of izatin – Dioxoindolinone – with anxiolytic and antidepressant action (according to preliminary studies). This article represents the results obtained from the study of the physical, chemical and physico-chemical properties of the studied compound: solubility, aspect of the solution, determination of the limit of non-specific impurities, losses through drying, determination of the melting point, as well as the elaboration of chemical reactions for identification. The results of the following research will be used for the future elaboration of the Analytical Documentation of Normation for Dioxoindolinone.

Synthesis of optic active hybrid compounds derivatives of oxindole has been performed via condensation of isatin with photosensible p-acetoazobenzene and transformational products of sclareol and leucine. It has been demonstrated that cytotoxicity of the sesquiterpenoide derivatives based on (+)-sclareol diminishes at change from the fife-membered lactamic ring to diole, as wellas at at the chage of nature of the bicyclic fragment, while increases at the change from the multisubstituted derivative of oxindole with a pyrrole fragment. The lowest cytotxicity has been detected for acetoacetate 11, which is comparable to that of the azoderivative 4а with values CC50 (cytotoxicity concentration 50 %) 0.0315 and CC50 = 0.0301 mМ, respectively, while the hybrid compound based on leucine has a twice lower toxicity (CC50 0.0116 mМ). It has been established that the compound 5а has affected the human immunodeficiency virus (HIV) replication at 24 times lower concentrations IC50 (inhibitory concentration 50 %) 0.0031 mМ than the antiretroviral agent didanosine (IC50 0.075 mМ), a reverstranscriptase inhibitor used in the HIV therapy.

Aminoalkylated carane-type aziridines were synthesized via epoxidation of (+)-3-carene by H2O2 solution (7%) in EtOAc catalyzed by α-Al2O3 nanoparticles, opening of the epoxide by NaN3, and cyclization of the azidoalcohol by Ph3P followed by condensation of the resulting aziridines with formalin and secondary amines. The cytotoxicity of the aminoalkylated aziridines with heteroorganic substituents increased on going from a five-membered pyrrolidine ring substituent to a six-membered piperidine ring and decreased sharply upon replacing a piperidine by a morpholine ring or increased on going to a piperazine ring. The structures of products were established using IR and NMR spectroscopy and an X-ray crystal structure analysis.

Herein we report the synthesis of some new 1H-1,2,4-triazole functionalized chromenols (3a–3n) via tandem reactions of 1-(alkyl/aryl)-2-(1H-1,2,4-triazole-1-yl) with salicylic aldehydes and the evaluation of their antifungal activity. In silico prediction of biological activity with computer program PASS indicate that the compounds have a high novelty compared to the known antifungal agents. We did not find any close analog among the over 580,000 pharmaceutical agents in the Cortellis Drug Discovery Intelligence database at the similarity cutoff of 70%. The evaluation of antifungal activity in vitro revealed that the highest activity was exhibited by compound 3k, followed by 3n. Their MIC values for different fungi were 22.1–184.2 and 71.3–199.8 µM, respectively. Twelve from fourteen tested compounds were more active than the reference drugs ketoconazole and bifonazole. The most sensitive fungus appeared to be Trichoderma viride, while Aspergillus fumigatus was the most resistant one. It was found that the presence of the 2-(tert-butyl)-2H-chromen-2-ol substituent on the 4th position of the triazole ring is very beneficial for antifungal activity. Molecular docking studies on C. albicans sterol 14α-demethylase (CYP51) and DNA topoisomerase IV were used to predict the mechanism of antifungal activities. According to the docking results, the inhibition of CYP51 is a putative mechanism of antifungal activity of the novel chromenol derivatives. We also showed that most active compounds have a low cytotoxicity, which allows us to consider them promising antifungal agents for the subsequent testing activity in in vivo assays.

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.

Three new hexanuclear Fe(III) coordination wheels [Fe6Cl6(L1)6]·5(MeCN) (1), [Na0.5Fe6Cl6(L1)6](N3)0.5·4.5(MeCN) (2), and [Fe6Cl6(L2)6]·2(MeCN) (3) have been synthesized with new prepared amino-acetonitrile derivatives 2-[bis(2-hydroxyethyl)amino]acetonitrile hydrochloride (H2L1) and 3-[bis(2-hydroxyethyl)amino]propanenitrile hydrochloride (H2L2). They were structurally characterized by single-crystal X-ray diffraction. Mosbauer spectroscopy and magnetic susceptibility measurements indicate dominant antiferromagnetic behavior between the Fe(III) centers.

1,2,4-Triazole is a very important scaffold in medicinal chemistry due to the wide spectrum of biological activities and mainly antifungal activity of 1,2,4-triazole derivatives. The main mechanism of antifungal action of the latter is inhibition of 14-alpha-demethylase enzyme (CYP51). The current study presents synthesis and evaluation of eight triazole derivatives for their antimicrobial activity. Docking studies to elucidate the mechanism of action were also performed. The designed compounds were synthesized using classical methods of organic synthesis. The in vivo evaluation of antimicrobial activity was performed by microdilution method. All tested compounds showed good antibacterial activity with MIC and MBC values ranging from 0.0002 to 0.0069 mM. Compound 2 h appeared to be the most active among all tested with MIC at 0.0002–0.0033 mM and MBC at 0.0004–0.0033 mM followed by compounds 2f and 2g. The most sensitive bacterium appeared to be Xanthomonas campestris while Erwinia amylovora was the most resistant. The evaluation of antifungal activity revealed that all compounds showed good antifungal activity with MIC values ranging from 0.02 mM to 0.52 mM and MFC from 0.03 mM to 0.52 mM better than reference drugs ketoconazole (MIC and MFC values at 0.28–1.88 mM and 0.38 mM to 2.82 mM respectively) and bifonazole (MIC and MFC values at 0.32–0.64 mM and 0.64–0.81 mM). The best antifungal activity is displayed by compound 2 h with MIC at 0.02–0.04 mM and MFC at 0.03–0.06 mM while compound 2a showed the lowest activity. The results showed that these compounds could be lead compounds in search for new potent antimicrobial agents. Docking studies confirmed experimental results.

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.

Two iron-based molten salts comprising an imidazolium and Schiff base were evaluated as catalysts for removal of carbamazepine (CBZ) from water. The catalysts were fully characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectrometry (EDX), nuclear magnetic resonance spectroscopy (NMR), electrospray ionisation–mass spectrometry (ESI–MS), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and nitrogen adsorption–desorption isotherms (BET). Additionally, the formation of photo-sensitized oxygen was investigated by spin-trapping using electron spin resonance (ESR). The catalytic activity in heterogeneous oxidation of the micropollutant (CBZ) was also evaluated. The effects of catalyst loading, pH, H2O2 dosage and UV light on the oxidation of the selected compound were investigated. After 15 min of UVA irradiation in the presence of 200 μM H2O2, CBZ was completely removed over both catalysts.

Interaction of N-ethyl isatin 3 with dimethyl acetylenedicarboxylate in the presence triphenylphosphine has led to good selectivity of methyl 1'-ethyl-4-methoxy-2',5-dioxo-5H-spiro[furan-2,3'-indoline]-3-carboxylate 4 formation. Similar yields of spirolactones 6,8 were obtained by addition of dimethyl acetylenedicarboxylate to 5-bromo functionalized isatins 5,7. However, reaction of N-butyl isatin 9 resulted in formation of an inseparable mixture of compounds. Treatment of N-benzyl isatin 10 and dimethyl acetylenedicarboxylate with triphenylphosphine proceeded with reduced selectivity of the spirooxindole 11 formation.

This paper is dedicated to the role of cyclodextrins in new formulations for the treatment of infections with Mycobacterium tuberculosis that are in the process of design and development. Cyclodextrins play the role of solubilizing agents and promoters of the antimycobacterial substances penetration inside the mycobacterial cell. Different formulations and their advantages and disadvantages are discussed.

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.

In the present review the data concerning selective synthetic transformations of isatins to 2-oxindoles, and studies of their biological activity are summarized.

Macrophages play an important role in the pathological development of different diseases. Therefore, macrophage targeting represents an important challenge in design of new medicines. This review gives a general presentation of small molecule-recognition concepts used for macrophage targeting. It describes mechanisms and systems for macrophage-targeted delivery, their obtaining and application.

Task-specific ionic liquids based on imidazolium cation containing carbonitrile, carboxyl, and alkyl chains have been employed in an attempt to design new functionalized liquids for solvent extraction of sulphur compounds from diesel fuel.

There is an increasing demand for novel metal-based complexes with biologically relevant molecules in technology and medicine. Three new Cu(II) coordination compounds with antifungal agent isoconazole (L), namely mononuclear complexes [CuCl2(L)2] (1), and [Cu(O2CMe)2(L)2]·2H2O (2) and coordination polymer [Cu(pht)(L)2]n (3) (where H2pht – o-phthalic acid) were synthesized and characterized by IR spectroscopy, thermogravimetric analysis and X-ray crystallography. X-ray analysis showed that in all complexes, the isoconazole is coordinated to Cu(II) centres by a N atom of the imidazole fragment. In complex 1, the square-planar environment of Cu(II) atoms is completed by two N atoms of isoconazole and two chloride ligands, whereas the Cu(II) atoms are coordinated by two N atoms from two isoconazole ligands and two O atoms from the different carboxylate residues: acetate in 2 and phthalate in 3. The formation of an infinite chain through the bridging phthalate ligand is observed in 3. The biosynthetic ability of micromycetes Aspergillus niger CNMN FD 10 in the presence of the prepared complexes 1–3 as well as the antifungal drug isoconazole were studied. Complexes 2 and 3 accelerate the biosynthesis of enzymes (β-glucosidase, xylanase and endoglucanase) by this fungus. Moreover, a simplified and improved method for the preparation of isoconazole nitrate was developed.

New optically active ionic liquids based on (+)-3-carene and 1H-imidazole were synthesized. Their structures were established.

Spirocyclopropanes: Only one out of eight possible stereoisomers was obtained in the asymmetric cascade cyclopropanation of alkylidene oxindoles with ethyl 2-chloroacetoacetate. Improved catalyst design ensured that spirocyclopropyl oxindoles featuring two quaternary centers were synthesized in high yield and high enantio- and diastereoselectivity (see scheme).

The present research paper is dedicated to the obtaining and physicochemical characterization of a highly potential anti-mycobacterial drug candidate with β-cyclodextrin (βCD). The active substance is a 1,3,4-oxadiazole derivative, 2-phenyl-5-{[(2-phenyl-1,3-dioxolan-2-yl)methyl]sulfanyl}-1,3,4-oxadiazole, further named DIOX. DIOX–βCD binary systems were obtained as a physical mixture and a lyophilized product with molar ratio between the main components equal to 1:1 and 1:2. The obtained systems were submitted to physicochemical characterization applying the following instrumental methods: infrared spectrometry, differential scanning calorimetry, and X-ray crystallographic analysis. Besides, a molecular modeling analysis has been performed. The research data suggested certain intermolecular interaction between DIOX and βCD, suggesting formation of a three-molecular inclusion complex DIOX:βCD, including one DIOX molecule and two molecules of βCD. The main parts of the DIOX molecule included in the hydrophobic cavity of the cyclodextrin molecules most probably are dioxolane cycle and two benzene rings.

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 Kohonen’s 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 requirement’s 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.

The paper summarizes literature data on occurrence of dihydroxyfumaric acid and its role in biological systems, as well as its chemical properties.

The synthesis and antiviral activity evaluation of new derivatives of 2-aminothiazole, 1,2,4-triazole, as well as oxindoles has been realized. The synthesized compounds exhibited different cytotoxicity, in particular, oxindols 4, 5 , 7 , 8 , 9, 10, 11, 12, 13, 58 as well as thiazole/triazole 73 and 75 turned out to be the most cytotoxic for MT-4 cell lines. The compounds 11, 12, 73, and 75 are more toxic than reference compound Efavirenz. As far as the antiviral activity is concerned, none of the title compounds turned out active against Reo-1, Sb-1, VSV, RSV, YFV and VV viruses. The results obtained against Bovine Viral Diarrhoea Virus (BVDV) showed that nine compounds (six from oxindol’s seria 6, 12, 13, 52, 56, 58 and three 73, 75, 77 of triazole homologues) resulted moderate active. Among all of them, the most potent compound was 52, with EC50 of 6.6 μM. Studies of effect of synthesized compounds against Coxsakie Virus (CVB-2) revealed that only two compounds, 13 and 73 exhibit moderate activity (EC50 >40 and >18 μM, respectively). It should be noticed that eleven compounds, 4, 5, 7, 8, 9, 10, 11, 12, 13, 58, and 75 showed moderate activity against HIV-1 (EC50 >16 – m >59μM).

Contemporary research for development of new antituberculosis drugs focuses on the following main areas: targeting of mycobacterial cell protein export systems, targeting cell wall integrity, intracellular energy processes targeting, targeting the mechanisms involved in the development of resistance, etc. Despite some obvious progress in development of new anti-TB drugs, a continuous research is still needed to overcome the problems connected with wide spread of MDR and XDR tuberculosis.

The paper describes the syntheses of new derivatives of dihydroxyfumaric acid and investigations of their antioxidant activities using the DPPH method.

Carane-type compounds have attracted attention in recent years due to their practical importance. This review is focused on describing the developments in the synthesis of trimethylbicyclo[4.1.0]heptanes and their unsaturated analogues from monoterpenes (+)-2- and (+)-3-carenes published mostly during the last decade.

Optically active chrysanthemic acid and its analogues have received considerable attention in recent years due to their practical importance. This review will focus on describing the developments in the synthesis of optically active chrysanthemic acid and its analogues. The transformation that will be covered includes the chemistry of enantiomerically pure 2,2-dimethyl 1,3-disubstituted cyclopropanes derived from monoterpene (+)-3-carene.

Ionic liquids are becoming widely used in chemical processes. Taking this into account we focus on recent advances in the synthesis and the investigation of 1H-imidazole derived ionic liquids. The fi rst part of this paper focuses on describing the developments in the synthesis and physical properties of 1,3-disubstituted imidazolium salts. The second part describes the application of these unique reagents, as catalysts and solvents in organic chemistry.

New effective synthesis of the chiral chinchoninic acids form (-)-α-pinene has been elaborated. It has been shown that, the considerable increase of the yield and purity of chiral acids is achieved applying the method of under phase transfer catalysis. New effective synthesis of the chiral chinchoninic acids form (-)-α-pinene has been elaborated. It has been shown that, the considerable increase of the yield and purity of chiral acids is achieved applying the method of under phase transfer catalysis.

Increasing longevity means that there is an increased likelihood of loss of cognitive functions and of incidence of dementias. There is thus a greater demand for cognition-enhancing (nootropic) drugs. Some such drugs are already available, but many display serious side-effects. We have designed, synthesized and tested a number of novel chemical entities that are predicted by the PASS software to be potential nootropic agents. The results have been subjected to QSAR (quantitative structure–activity relationship) analysis, and good QSAR correlations, with external validation, have been obtained, which can be used predictively to guide design of additional potential cognition-enhancers.