Extremely Slow Thermally-Induced Spin Crossover in the Two-Dimensional Network [Fe(bbtr)3 ](BF4 )2.

Cooling [Fe(bbtr)3 ](BF4 )2 (bbtr=1,4-di(1,2,3-triazol-1-yl)butane) triggers very slow spin crossover below 80 K (T1/2 ↓ =76 K). The spin crossover (SCO) is accompanied by a hysteresis loop (T1/2 ↑ =89 K). In contrast to isostructural perchlorate analogue [Fe(bbtr)3 ](ClO4 )2 in which spin crossover during cooling is preceded by phase transition at TPT =126 K in tetrafluoroborate phase transition does not occur to the beginning of spin crossover (80 K). Studies of mixed crystals [Fe(bbtr)3 ](BF4 )2(1-x) (ClO4 )2x (0.5≤x≤0.9) showed that a phase transition precedes spin crossover, however, for x≅0.46 intersection of T1/2 (x) and TPT (x) dependencies takes place. The application of pressure of 1 GPa shifts the spin crossover in [Fe(bbtr)3 ](BF4 )2 to a temperature above 270 K. High-pressure studies of neat tetrafluoroborate and perchlorate, as well as mixed crystals [Fe(bbtr)3 ](BF4 )2(1-x) (ClO4 )2x (0.1≤x≤0.9), revealed that at 295 K P1/2 value changes linearly with x indicating similar mechanism of spin crossover under elevated pressure in all systems under investigation. Variable pressure single crystal X-ray diffraction studies confirmed that in contrast to thermally induced spin crossover undergoing differently in tetrafluoroborate and perchlorate an application of high pressure removes this differentiation leading to a similar mechanism depending at first on start spin crossover and then P-3→P-1 phase transition occurs. In this report we have shown that 2D coordination polymer [Fe(bbtr)3 ](BF4 )2 (bbtr=1,4-di(1,2,3-triazol-1-yl)butane) treated to date as spin crossover silent shows thermally induced spin crossover phenomenon. Spin crossover in tetrafluoroborate is extremely slow. Determination of the spin crossover curve required carrying measurement in the settle mode-cooling from 85 to 70 K took about 600 h (average velocity of change of temperature ca. 0.0004 K/min).

Evaluation of anticancer activity of novel platinum(II) bis(thiosemicarbazone) complex against breast cancer.

The study aims to synthesize a novel bis(thiosemicarbazone) derivative based on platinum (thioPt) and evaluate its anticancer properties against MFC-7 and MDA-MB-231 breast cancer cells. A new platinum complex was synthesised by reacting K2PtCl4 with 2,2'-(1,2-diphenylethane-1,2-diylidene)bis(hydrazine-1-carbothioamide) in ethanol in the presence of K2CO3. In the obtained complex, the platinum atom is coordinated by a conjugated system = N-NC-S-The structures of the new compound were characterised using NMR spectroscopy, HR MS, IR, and X-ray structural analysis. The obtained results of the cytotoxicity assay indicate that compound thioPt had potent anticancer activity (MCF-7: 61.03 ± 3.57 µM, MDA-MB-231: 60.05 ± 5.40 µM) with less toxicity against normal MCF-10A breast epithelial cells, even compared to the reference compound (cisplatin). In addition, subsequent experiments found that thioPt induces apoptosis through both an extrinsic (↑caspase 8 activity) and intrinsic (↓ΔΨm) pathway, which ultimately leads to an increase in active caspase 3/7 levels. The induction of autophagy and levels of proteins involved in this process (LC3A/B and Beclin-1) were examined in MCF-7 and MDA-MB-231 breast cancer cells exposed to tested compounds (thio, thioPt, cisPt) at a concentration of 50 µM for 24 h. Based on these results, it can be concluded that thio and thioPt do not significantly affect the autophagy process. This demonstrates their superiority over cisplatin, which can stimulate cancer cell survival through its effect on stimulation of autophagy.

Synthesis and Spectroscopic Characterization of Selected Water-Soluble Ligands Based on 1,10-Phenanthroline Core.

Water-soluble ligands based on a 1,10-phenanthroline core are relatively poorly studied compounds. Developing efficient and convenient syntheses of them would result in new interesting applications because of the importance of 1,10-phenanthrolines. In this manuscript, we describe novel and practical ways to introduce a carboxyl and, for the first time, a phenol and dithiocarboxyl group under mild reaction conditions. This strategy enables highly efficient and practical synthesis of suitable organosulfur compounds with high added value, high chemoselectivity, and a broad substrate range. We present the selective conversion of a hydroxydialdehyde in the form of 10-hydroxybenzo[h]quinoline-7,9-dicarbaldehyde into its derivative, unique hydroxydicarboxylic acid, by an oxidation procedure, giving 10-hydroxybenzo[h]quinoline-7,9-dicarboxylic acid. A similar procedure resulted in the formation of 9-methyl-1,10-phenanthroline-2-carboxylic acid by oxidation of commercially available neocuproine. An alternative method of obtaining 1,10-phenanthroline derivatives possessing carboxylic acid group can be based on the hydrolysis of ester or nitrile groups; however, this synthesis leads to unexpected products. Moreover, we apply Perkin condensation to synthesize a vinyl (or styryl) analog of 1,10-phenanthroline derivatives with phenol function. This reaction also demonstrates a new, simple, and efficient strategy for converting methyl derivatives of 1,10-phenanthroline. We anticipate that the new way of converting methyl will find wide application in chemical synthesis.

Surprising Solid-State ESIPT Emission from Apparently Ordinary Salicyliden Glycinates Schiff Bases.

Excited-State Intramolecular Photon Transfer (ESIPT) is known for the geometry-related phenolic and imine groups. The Schiff bases formed upon condensation of salicyl aldehyde and glycine led to the formation of ESIPT models. A series of alkali metal salicyliden glycinates were analyzed by X-ray diffraction of their monocrystals and spectroscopy measurements. The X-ray analysis revealed varied hydration levels between the salts. They adapted trans geometry on the imine groups and mostly anticlinal conformation with the neighboring atoms, which is different from the other structurally-related compounds in literature. Fluorescence of these compounds was found for the crystalline forms only. Protonation of the imine nitrogen atom and further proton distribution was consistent with the ESIPT theory, which also explained the observed fluorescence with the highest Stokes shift of 10,181 cm-1 and 10.1% of fluorescence quantum yield for the sodium salt.

Biochemical, Structural Analysis, and Docking Studies of Spiropyrazoline Derivatives.

In this study, we evaluated the antiproliferative potential, DNA damage, crystal structures, and docking calculation of two spiropyrazoline derivatives. The main focus of the research was to evaluate the antiproliferative potential of synthesized compounds towards eight cancer cell lines. Compound I demonstrated promising antiproliferative properties, especially toward the HL60 cell line, for which IC50 was equal to 9.4 µM/L. The analysis of DNA damage by the comet assay showed that compound II caused DNA damage to tumor lineage cells to a greater extent than compound I. The level of damage to tumor cells of the HEC-1-A lineage was 23%. The determination of apoptotic and necrotic cell fractions by fluorescence microscopy indicated that cells treated with spiropyrazoline-based analogues were entering the early phase of programmed cell death. Compounds I and II depolarized the mitochondrial membranes of cancer cells. Furthermore, we performed simple docking calculations, which indicated that the obtained compounds are able to bind to the PARP1 active site, at least theoretically (the free energy of binding values for compound I and II were -9.7 and 8.7 kcal mol-1, respectively). In silico studies of the influence of the studied compounds on PARP1 were confirmed in vitro with the use of eight cancer cell lines. The degradation of the PARP1 enzyme was observed, with compound I characterized by a higher protein degradation activity.

Synthesis and Spectroscopic Characterization of Selected Phenothiazines and Phenazines Rationalized Based on DFT Calculation.

Two unique structures were isolated from the phosphorylation reaction of 10H-phenothiazine. The 5,5-dimethyl-2-(10H-phenothiazin-10-yl)-1,3,2-dioxaphosphinane 2-oxide (2a) illustrates the product of N-phosphorylation of phenothiazine. Moreover, a potential product of 2a instability, a thiophosphoric acid 2b, was successfully isolated and structurally characterized. Molecule 2a, similarly to sulfoxide derivative 3, possesses interesting phosphorescence properties due to the presence of d-pπ bonds. The X-ray, NMR, and DFT computational studies indicate that compound 2a exhibits an anomeric effect. Additionally, the syntheses of selected symmetrical and unsymmetrical pyridine-embedded phenazines were elaborated. To compare the influence of phosphorus and sulfur atoms on the structural characteristics of 10H-phenothiazine derivatives, the high-quality crystals of (4a,12a-dihydro-12H-benzo[5,6][1,4]thiazino[2,3-b]quinoxalin-12-yl)(phenyl)methanone (1) and selected phenazines 5,12-diisopropyl-3,10-dimethyldipyrido[3,2-a:3',2'-h]phenazine (5) and 5-isopropyl-N,N,3-trimethylpyrido[3,2-a]phenazin-10-amine (6a) were obtained. The structures of molecules 1, 2a, 2-mercapto-5,5-dimethyl-1,3,2-dioxaphosphinane 2-oxide (2b), 3,7-dinitro-10H-phenothiazine 5-oxide (3), 5 and 6a were determined by single-crystal X-ray diffraction measurements.

Synthesis, Spectroscopy, Single-Crystal Structure Analysis and Antibacterial Activity of Two Novel Complexes of Silver(I) with Miconazole Drug.

In a previous article, we reported on the higher toxicity of silver(I) complexes of miconazole [Ag(MCZ)2NO3 (1)] and [Ag(MCZ)2ClO4 (2)] in HepG2 tumor cells compared to the corresponding salts of silver, miconazole and cisplatin. Here, we present the synthesis of two silver(I) complexes of miconazole containing two new counter ions in the form of Ag(MCZ)2X (MCZ = 1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole]; X = BF4- (3), SbF6- (4)). The novel silver(I) complexes were characterized by elemental analysis, 1H NMR, 13C NMR and infrared (IR) spectroscopy, electrospray ionization (ESI)-MS spectrometry and X-ray-crystallography. In the present study, the antimicrobial activity of all obtained silver(I) complexes of miconazole against six strains of Gram-positive bacteria, five strains of Gram-negative bacteria and yeasts was evaluated. The results were compared with those of a silver sulfadiazine drug, the corresponding silver salts and the free ligand. Silver(I) complexes exhibited significant activity against Gram-positive bacteria, which was much better than that of silver sulfadiazine and silver salts. The highest antimicrobial activity was observed for the complex containing the nitrate counter ion. All Ag(I) complexes of miconazole resulted in much better inhibition of yeast growth than silver sulfadiazine, silver salts and miconazole. Moreover, the synthesized silver(I) complexes showed good or moderate activity against Gram-negative bacteria compared to the free ligand.

Direct Amination of Nitroquinoline Derivatives via Nucleophilic Displacement of Aromatic Hydrogen.

The vicarious nucleophilic substitution of hydrogen (VNS) reaction in electron-deficient nitroquinolines was studied. Properties of all new products have been characterized by several techniques: MS, HRMS, FTIR, GC-MS, electronic absorption spectroscopy, and multinuclear NMR. The structures of 4-chloro-8-nitroquinoline, 8-(tert-butyl)-2-methyl-5-nitroquinoline, 9-(8-nitroquinolin-7-yl)-9H-carbazole and (Z)-7-(9H-carbazol-9-yl)-8-(hydroxyimino)quinolin-5(8H)-one were determined by single-crystal X-ray diffraction measurements. The 9-(8-nitroquinolin-7-yl)-9H-carbazole and (Z)-7-(9H-carbazol-9-yl)-8-(hydroxyimino)quinolin-5(8H)-one illustrate the nitro/nitroso conversion within VNS reaction. Additionally, 9-(8-isopropyl-2-((8-isopropyl-2-methyl-5-nitroquinolin-6-yl)methyl)-5-nitrosoquinolin-6-yl)-9H-carbazole is presented as a double VNS product. It is postulated that the potassium counterion interacts with the oxygen on the nitro group, which could influence nucleophile attack in that way.

Molecular Structure, In Vitro Anticancer Study and Molecular Docking of New Phosphate Derivatives of Betulin.

A series of 30-diethylphosphate derivatives of betulin were synthesized and evaluated for their in vitro cytotoxic activity against human cancer cell lines, such as amelanotic melanoma (C-32), glioblastoma (SNB-19), and two lines of breast cancer (T47D, MDA-MB-231). The molecular structure and activities of the new compounds were also compared with their 29-phosphonate analogs. Compounds 7a and 7b showed the highest activity against C-32 and SNB-19 cell lines. The IC50 values for 7a were 2.15 and 0.91 µM, and, for 7b, they were 0.76 and 0.8 µM for the C-32 and SNB-19 lines, respectively. The most potent compounds, 7a and 7b, were tested for their effects on markers of apoptosis, such as H3, TP53, BAX, and BCL-2. For the whole series of phosphate derivatives, a lipophilicity study was performed, and the ADME parameters were calculated. The most active products were docked to the active site of the EGFR protein. The relative binding affinity of selected phosphate betulin derivatives toward EGFR was compared with standard erlotinib on the basis of ChemScore and KDEEP score. Positively, all derivatives docked inside the cavity and showed significant interactions. Moreover, a molecular dynamics study also reveals that ligands 7a,b form stable complexes and the plateau phase started after 7 ns.

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity.

Amino- and polyaminophthalazinones were synthesized by the palladium-catalyzed amination (alkyl- and arylamines, polyamines) of 4-bromophthalazinones in good yields. The coordinating properties of selected aminophthalazinones towards Cu(II) ions were investigated and the participation of the nitrogen atoms in the complexation of the metal ion was shown. A biological screening of the potential cytotoxicity of selected synthesized compounds on HT-29 and PC-3 cell lines, as well as on the L-929 cell line, proved that some amino derivatives of phthalazinone show interesting anticancer activities. The detailed synthesis, spectroscopic data, and biological assays are reported.

Spatiotemporal Studies of the One-Dimensional Coordination Polymer [Fe(ebtz)2 (C2 H5 CN)2 ](BF4 )2 : Tug of War between the Nitrile Reorientation Versus Crystal Lattice as a Tool for Tuning the Spin Crossover Properties*.

Reaction of 1,2-di(tetrazol-2-yl)ethane (ebtz) with Fe(BF4 )2 ⋅6 H2 O in different nitriles yields one-dimensional coordination polymers [Fe(ebtz)2 (RCN)2 ](BF4 )2 ⋅nRCN (n=2 for R=CH3 (1) and n=0 for R=C2 H5 (2) C3 H7 (3), C3 H5 (4), CH2 Cl (5)) exhibiting spin crossover (SCO). SCO in 1 and 3-5 is complete and occurs above 160 K. In 2, it is shifted to lower temperatures and is accompanied by wide hysteresis (T1/2 ↓ =78 K, T1/2 ↑ =123 K) and proceeds extremely slowly. Isothermal (80 K) time-resolved single-crystal X-ray diffraction studies revealed a complex nature for the HS→LS transition in 2. An initial, slow stage is associated with shrinkage of polymeric chains and with reduction of volume at 77 % (in relation to the difference between cell volumes VHS -VLS ) whereas only 16 % of iron(II) ions change spin state. In the second stage, an abrupt SCO occurs, associated with breathing of the crystal lattice along the direction of the Fe-nitrile bonds, while the nitriles reorient. HS→LS switching triggered by light (808 nm) reveals the coupling of spin state and nitrile orientation. The importance of this coupling was confirmed by studies of [Fe(ebtz)2 (C2 H5 CN/C3 H7 CN)2 ](BF4 )2 mixed crystals (2 a, 2 b), showing a shift of T1/2 to higher values and narrowing of the hysteresis loop concomitant with an increase of the fraction of butyronitrile. This increase reduces the capability of nitrile molecules to reorient. Density functional theory (DFT) studies of models of 1-5 suggest a particular possibility of 2 to adopt a low (140-145°) value of its Fe-N-C(propionitrile) angle.

Synthesis, Spectroscopy, Light Stability, Single-Crystal Analysis, and In Vitro Cytotoxic Activity on HepG2 Liver Cancer of Two Novel Silver(I) Complexes of Miconazole.

Two novel silver(I) complexes of the biologically active ligand miconazole in the form of Ag(MCZ)2X (MCZ = 1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole]; X = NO3- (1), ClO4- (2)) were synthesized and fully characterized. The complexes were obtained by reactions of Ag(I) salts with miconazole (MCZ). Silver(I) complexes were characterized by elemental analysis, 1H-NMR and infrared (IR) spectroscopy, electrospray ionization (ESI)-MS spectrometry, and X-ray-crystallography. This work also presents a cytotoxicity study of the silver(I) complexes of miconazole and appropriate silver(I) salts using Balb/c 3T3 and HepG2 cell lines. The cytotoxicity of the compounds was assessed based on four biochemical endpoints: lysosomal activity (neutral red uptake (NRU) assay), mitochondrial activity (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay), total protein content (TPC assay), and cellular membrane integrity (lactate dehydrogenase (LDH) assay). The cancer HepG2 cells were more sensitive to the complexes tested, and the most affected endpoint was cellular membrane damage compared to Balb/c 3T3 fibroblasts. Moreover, study complexes inhibited the growth of cancer cells at submicromolecular concentrations (0.26-0.47 µM) lower than that required for the anticancer agent, cisplatin, in MTT, NRU, and TPC assays. Both complexes were characterized by higher toxicity to human cancer cells (HepG2) than silver(I) salts and the free ligand. Combination of Ag(I) salts with miconazole is associated with the marked improvement of cytotoxic activities that can be considered as the significant point in the construction of a new generation of antineoplastic agents.

Zinc(II) Complexes with Amino Acids for Potential Use in Dermatology: Synthesis, Crystal Structures, and Antibacterial Activity.

The multifunctional profile of Zn2+ has influenced its great popularity in various pharmaceutical, food, and cosmetic products. Despite the use of different inorganic and organic zinc derivatives, the search for new zinc-containing compounds with a safer skin profile still remains an open issue. The present paper describes the synthesis, structural characterization, and antibacterial activity of zinc(II) complexes with proteinogenic amino acids as potential candidates for dermatological treatments. The obtained complexes are of the general formula [Zn(AA)2], where AA represents an amino acid (L-Glu, Gly, L-His, L-Pro, L-Met, and L-Trp). Their synthesis was designed in such a way that the final bis(aminoacidate) zinc(II) complexes did not contain any counter-ions such as Cl-, NO3-, or SO42- that can cause some skin irritations. The chemical structure and composition of the compounds were identified by 1H NMR spectroscopy and elemental analysis, and four were also characterized by single-crystal X-ray diffraction. The Hirshfeld surface analysis for the Zn2+ metallic center helped to determine its coordination number and geometry for each complex. Finally, the antibacterial properties of the complexes were determined with respect to three Gram-positive strains, viz. Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, and Streptococcus pyogenes ATCC 19615, and two Gram-negative bacteria, viz. Escherichia coli ATCC 25992 and Pseudomonas aeruginosa ATCC 27853, and were compared with the activity of zinc 2-pirrolidone 5-carboxylate (ZnPCA), commonly applied in dermatology. It was found that the Zn(II) complexes with methionine and glycine exhibited a higher antibacterial activity than the tested standard, and the antimicrobial properties of complex with Trp were satisfactory. The results of the antimicrobial activity examination allow us to postulate that the obtained zinc complexes might become new active substances for use in dermatological products.

Synthesis, Electrochemical and Spectroscopic Characterization of Selected Quinolinecarbaldehydes and Their Schiff Base Derivatives.

A new approach to the synthesis of selected quinolinecarbaldehydes with carbonyl groups located at C5 and/or in C7 positions is presented in this paper in conjunction with spectroscopic characterization of the products. The classical Reimer-Tiemann, Vilsmeier-Haack and Duff aldehyde synthesis methods were compared due to their importance. Computational studies were carried out to explain the preferred selectivity of the presented formylation transformations. A carbene insertion reaction based on Reimer-Tiemann methodology is presented for making 7-bromo-8-hydroxyquinoline-5-carbaldehyde. Additionally, Duff and Vilsmeier-Haack reactions were used in the double formylation of quinoline derivatives and their analogues benzo[h]quinolin-10-ol, 8-hydroxy-2-methylquinoline-5,7-dicarbaldehyde, 8-(dimethylamino) quinoline-5,7-dicarbaldehyde and 10-hydroxybenzo[h]quinoline-7,9-dicarbaldehyde. Four Schiff base derivatives of 2,6-diisopropylbenzenamine were prepared from selected quinoline-5-carbaldehydes and quinoline-7-carbaldehyde by an efficient synthesis protocol. Their properties have been characterized by a combination of several techniques: MS, HRMS, GC-MS, FTIR, electronic absorption spectroscopy and multinuclear NMR. The electrochemical properties of 8-hydroxy-quinoline-5-carbaldehyde, 6-(dimethylamino)quinoline-5-carbaldehyde and its methylated derivative were investigated, and a strong correlation between the chemical structure and obtained reduction and oxidation potentials was found. The presence of a methyl group facilitates oxidation. In contrast, the reduction potential of methylated compounds was more negative comparing to non-methylated structure. Calculations of frontier molecular orbitals supported the finding. The structures of 8-hydroxy-2-methylquinoline-5,7-dicarbaldehyde and four Schiff bases were determined by single-crystal X-ray diffraction measurements.

Biological Evaluation of 3-Benzylidenechromanones and Their Spiropyrazolines-Based Analogues.

A series of 3-benzylidenechrmanones 1, 3, 5, 7, 9 and their spiropyrazoline analogues 2, 4, 6, 8, 10 were synthesized. X-ray analysis confirms that compounds 2 and 8 crystallize in a monoclinic system in P21/n space groups with one and three molecules in each asymmetric unit. The crystal lattice of the analyzed compounds is enhanced by hydrogen bonds. The primary aim of the study was to evaluate the anti-proliferative potential of 3-benzylidenechromanones and their spiropyrazoline analogues towards four cancer cell lines. Our results indicate that parent compounds 1 and 9 with a phenyl ring at C2 have lower cytotoxic activity against cancer cell lines than their spiropyrazolines analogues. Analysis of IC50 values showed that the compounds 3 and 7 exhibited higher cytotoxic activity against cancer cells, being more active than the reference compound (4-chromanone or quercetin). The results of this study indicate that the incorporation of a pyrazoline ring into the 3-arylideneflavanone results in an improvement of the compounds' activity and therefore it may be of use in the search of new anticancer agents. Further analysis allowed us to demonstrate the compounds to have a strong inhibitory effect on the cell cycle. For instance, compounds 2, 10 induced 60% of HL-60 cells to be arrested in G2/M phase. Using a DNA-cleavage protection assay we also demonstrated that tested compounds interact with DNA. All compounds at the concentrations corresponding to cytotoxic properties are not toxic towards red blood cells, and do not contribute to hemolysis of RBCs.

Sliding Polymeric Layers and Anion Displacement Coupled with Spin Crossover in Two-Dimensional Networks of [Fe(hbtz)2 (CH3 CN)2 ](BF4 )2.

The abrupt high spin (HS)→low spin (LS) transition (T↓ 1/2 =136 K) in [Fe(hbtz)2 (CH3 CN)2 ](BF4 )2 (hbtz=1,6-di(tetrazol-2-yl)hexane) is finished at 100 K and further thermal treatment influences the spin crossover. Subsequent heating involves a change of the spin state in the same way (T↑ 1/2 =136 K) on cooling. In contrast, cooling below 100 K triggers different behavior and T↑ 1/2 is shifted to 170 K. The extraordinary structural changes that occurred below 100 K are responsible for the observed diversity of properties. A unique feature of the low-temperature phase is the rebuilding of the anion network expressed by a shift of anions inside the polymeric layer at a distance of 1.2 Šas well as the relative shift of neighboring layers at over 4 Å. These structural alterations, connected with a phase transition, become the origin of the strain, which in most cases causes crystal cleaving. In a sample composed from crystals crushed as a result of the phase transition or as a result of mechanical crumbling, the hysteresis loop vanishes; however, annealing the sample allows to its partial restoration. A replacement of acetonitrile by other nitriles leads to preservation of the polymeric structure and spin crossover, but no phase transition follows.

New phosphate derivatives of betulin as anticancer agents: Synthesis, crystal structure, and molecular docking study.

Betulin derivatives exhibit an antiproliferative activity and have been tested for many cancer cell lines. This paper describes a new series of 3-phosphate derivatives of betulin bearing different substituents at C28 position. The synthesized compounds were tested in vitro for their antiproliferative effect against human leukemia (MV-4-11 and CCRF/CEM), lung carcinoma (A549), prostate cancer (DU 145), melanoma (Hs 294T) cell lines, and murine leukemia P388. To explore the possible mechanism of anticancer activity for the most in vitro active compounds (4, 5, 7 and 8) and betulin, molecular docking was performed to the binding sites of potential anticancer targets, described for the various triterpene derivatives, including topoisomerase I and II, epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGFR), transcription factor NF-κB, anti-apoptotic protein Bcl-2 and peroxisome proliferator-activated receptor (PPARγ). According to the results of the docking, the best fit to the binding pocket of PPARγ was shown by compound 4.

Synthesis, Spectroscopic Analysis and Assessment of the Biological Activity of New Hydrazine and Hydrazide Derivatives of 3-Formylchromone.

The hydrazine and hydrazide derivatives of benzo-γ-pyrones with fluorine substituents remain an unexplored group of chemical compounds. This preliminary study reports the synthesis, structural assessment, initial microbiological screening and biological testing of the synthesized compounds on cell lines using the XTT-assay. A series of 10 novel hydrazine and hydrazide derivatives of 3-formylchromone were synthesized and their structures determined. Structural assessment consisted of elemental analysis, IR, ¹H-NMR, 13C-NMR, MS and crystallographic studies. Antimicrobial activity was tested on standard strains representing different groups of microorganisms. The tested compounds were found to inhibit microbial growth. Concentrations of 0.01⁻1250 µmol/L were found to influence cell proliferation, demonstrating antiproliferative and stimulation of proliferation against two cell lines: the L929 cell line (mouse fibroblast cell line) and the EA.hy926 cell line (the human umbilical vein, somatic cell hybrid).

Interaction of Arylidenechromanone/Flavanone Derivatives with Biological Macromolecules Studied as Human Serum Albumin Binding, Cytotoxic Effect, Biocompatibility Towards Red Blood Cells.

The aim of this study was to determine the cytotoxic effect of 3-arylidenechromanone (1) and 3arylideneflavanone (2) on HL-60 and NALM-6 cell lines (two human leukemia cell lines) and a WM-115 melanoma cell line. Both compounds exhibited high cytotoxic activity with higher cytotoxicity exerted by compound 2, for which IC50 values below 10 µM were found for each cell line. For compound 1, the IC50 values were higher than 10 µM for HL-60 and WM-115 cell lines, but IC50 < 10 µM was found for the NALM-6 cell line. Both compounds, at the concentrations close to IC50 (concentration range: 5⁻24 µM/L for compound 1 and 6⁻10 µM/L for compound 2), are not toxic towards red blood cells. The synthesized compounds were characterized using spectroscopic methods ¹H- and 13C-NMR, IR, MS, elemental analysis, and X-ray diffraction. The lipophilicity of both synthesized compounds was determined using an RP-TLC method and the logP values found were compared with the theoretical ones taken from the Molinspiration Cheminformatics (miLogP) software package. The mode of binding of both compounds to human serum albumin was assessed using molecular docking methods.

Synthesis, Structure and Cytotoxic Activity of Mono- and Dialkoxy Derivatives of 5,8-Quinolinedione.

A series of 5,8-quinolinedione derivatives containing one or two alkoxy groups was synthesized and characterized by ¹H- and (13)C-NMR, IR and MS spectra. X-ray diffraction was used to investigate the crystal structures of 6-chloro-7-(2-cyjanoethoxy)-5,8-quinolinedione and 6,7-di(2,2,2-trifloroethoxy)-5,8-quinolinedione. All studied compounds were tested in vitro for their antiproliferative activity against three human cancer cell lines and human normal fibroblasts. Most of the compounds showed higher cytotoxicity than the starting compound, 6,7-dichloro-5,8-quinolinedione, and cisplatin, which was used as a reference agent.