Dual activity of indolin-2-ones containing an arylidene motif: DNA and BSA interaction.

Applying a multistep approach, novel indolin-2-ones (IND) that possess an arylidene motif have been synthesized. Eight compounds were chosen for different biological tests (antimicrobial and cytotoxicity). IND containing 2-thienyl (4h) fragment have been found to exhibit good antimicrobial activity against B. cereus. Molecules that have 3-aminophenyl (4d) or 2-pyridyl (4g) groups have shown the best antifungal activities against all tested fungi. These compounds have also been noticed as promising pharmaceuticals against MCF-7 cancer cell lines. Experimental outcomes from the investigation of the interaction of 4d with DNA implied its moderate binding to DNA (KSV = 1.35 × 104 and 3.05 × 104 M-1 for EB and Hoechst binder, respectively). However, considerably stronger binding of 4d to BSA has been evidenced (Ka = 6.1 × 106 M-1). In summary, IND that contains m-aminobenzylidene fragment (4d) exhibits a good dual biological activity making it a promising candidate for further investigation in the drug discovery sector.

Synthesis, characterization, and biological activity of some 2,4-diketo esters containing dehydrozingerone fragment: DNA and protein binding study.

Due to the increased resistance to antibiotics, in recent years there has been a growing interest in the discovery of new antimicrobial agents from different sources. Bacteria that are resistant to most antibiotics are a global public health concern. In order to find a new antimicrobial drug, we synthesized a small series of 2,4-diketo esters and tested them on some gram-positive and gram-negative bacterial strains. Two compounds showed very good antibacterial activity against Staphylococcus aureus and Bacillus subtilis, respectively. Trichophyton mentagrophytes proved to be the most sensitive of the tested species regarding antifungal activity. Also, research was conducted on the biomolecule of bovine serum albumin. Examining these interactions, we concluded that all compounds have the appropriate binding affinity for bovine serum albumin, which is vital. Furthermore, to investigate the potential antitumor activity, interactions with DNA were carried out. Examining the interactions between our compounds and DNA using fluorescence, we concluded that all but one of the compounds interacts with the DNA molecule by intercalation. In addition, a molecular docking study was performed to investigate the binding mode of the tested compounds to DNA and bovine serum albumin. In conclusion, all the results indicate a great potential for the future application of these compounds in clinical practice in the future.

Synthesis, Characterization, and Biological Evaluation of Meldrum's Acid Derivatives: Dual Activity and Molecular Docking Study.

In the presented study, eight novel Meldrum's acid derivatives containing various vanillic groups were synthesized. Vanillidene Meldrum's acid compounds were tested against different cancer cell lines and microbes. Out of nine, three showed very good biological activity against E. coli, and HeLa and A549 cell lines. It is shown that the O-alkyl substituted derivatives possessed better antimicrobial and anticancer activities in comparison with the O-acyl ones. The decyl substituted molecule (3i) has the highest activity against E. coli (MIC = 12.4 µM) and cancer cell lines (HeLa, A549, and LS174 = 15.7, 21.8, and 30.5 µM, respectively). The selectivity index of 3i is 4.8 (HeLa). The molecular docking study indicates that compound 3i showed good binding affinity to DNA, E. coli Gyrase B, and topoisomerase II beta. The covalent docking showed that 3i was a Michael acceptor for the nucleophiles Lys and Ser. The best Eb was noted for the topoisomerase II beta-LYS482-3i cluster.

Investigation of the radical scavenging potential of vanillin-based pyrido-dipyrimidines: experimental and in silico approach.

Antioxidants have a significant contribution in the cell protection against free radicals which may induce oxidative stress, and permanently damage the cells causing different disorders such as tumors, degenerative diseases, and accelerated aging. Nowadays, a multi-functionalized heterocyclic framework plays an important role in drug development, and it is of great importance in organic synthesis and medicinal chemistry. Encouraged by the bioactivity of the pyrido-dipyrimidine scaffold and vanillin core, herein, we made an effort to thoroughly investigate the antioxidant potential of the vanillin-based pyrido-dipyrimidines A-E to reveal novel promising free radical inhibitors. The structural analysis and the antioxidant action of the investigated molecules were performed in silico by DFT calculations. Studied compounds were screened for their antioxidant capacity using in vitro ABTS and DPPH assays. All the investigated compounds showed remarkable antioxidant activity, especially derivative A exhibiting inhibition of free radicals at the IC50 value (ABTS and DPPH assay 0.1 mg ml-1 and 0.081 mg ml-1, respectively). Compound A has higher TEAC values implying its stronger antioxidant activity compared to a trolox standard. The applied calculation method and in vitro tests confirmed that compound A has a strong potential against free radicals and may be a novel candidate for application in antioxidant therapy.

Anticancer potential of some ß-diketonates: DNA interactions, protein binding properties, and molecular docking study.

With the goal to discover a new antitumor drug with the better or similar effects to existing, a small series of ß-diketonate was tested on a cisplatin-resistant MDA-MB-231 and HeLa tumor cell lines, and nontumor MRC-5 cell line. All compounds showed notable cytotoxicity against both tumor cell lines and good selectivity. Importantly, ß-diketonates displayed greater selectivity than cisplatin, which is the crucial factor for a new antitumor drug candidate. Further, investigations with biomacromolecules such as DNA and serum albumin were performed. Investigations showed that tested compounds bind to DNA through intercalation and have appropriate affinity for binding to bovine serum albumin. In addition, the molecular docking study was performed to investigate more specifically the sites and binding mode of tested ß-diketonate to DNA or bovine serum albumin. In conclusion, all results indicated the big potential of these compounds for application in clinical practice in future.

Synthesis, characterization, antitumor potential, and investigation of mechanism of action of copper(ii) complexes with acylpyruvates as ligands: interactions with biomolecules and kinetic study.

Considering the urgency of finding a cure for vicious diseases such as tumors, we have synthesized and characterized a small series of new copper(ii) complexes with biologically important ligands such as acylpyruvate. In addition to this, we used another four copper(ii) complexes, with ligands of the same type to examine the antitumor potential. The antitumor potential of the copper(ii) complexes was examined on three tumor cell lines and one normal human cell line using the MTT assay. All seven tested complexes showed very good cytotoxic effects. Two copper complexes that showed the best antitumor potential were selected for further testing that showed the best potential for potential application in the future. The mechanism of activity of these complexes was examined in detail using tests such as cell cycle, ROS level, oxidative DNA damage, and proteins related to hypoxia analysis. In addition, we examined the binding abilities of these complexes with biomolecules (Guo, Ino, 5'-GMP, BSA, and DNA). The results showed that the tested compounds bind strongly to DNA molecules through intercalation. Also, it has been shown that the tested compounds adequately bind to the BSA molecule, which indicates an even greater potential for some future application of these compounds in clinical practice.

Synthesis, Characterization, and Biological Evaluation of Tetrahydropyrimidines: Dual-Activity and Mechanism of Action.

In this paper, the synthesis, characterization, and biological evaluation of the novel tetrahydropyrimidines-THPMs are described. THPMs are well-known for wide pharmacological activities such as antimicrobial, anticancer, antiviral, etc. This research includes obtained results of in vitro antimicrobial, anticancer, and α-glucosidase inhibitory activities of the eleven novel THPMs. An antibiotic assessment was done against five bacteria (two Gram-positive and three Gram-negative) and five fungi by determining the minimal inhibitory concentration (MIC), using the broth tube dilution method. The most active antibacterial compounds were 4a, 4b, and 4d, while the best antifungal activity was shown by 4e, 4f, and 4k. The lowest MIC value (0.20 mg/mL) was measured for 4e, 4f, and 4k against the Trichophyton mentagrophytes. Moreover, examining the α-glucosidase inhibitory activity revealed the compound 4g as the one with the best activity. The cytotoxic activity was performed on the tumor cell lines (HeLa, K562, and MDA-MB-231) and normal cells (MRC-5). The best antitumor activity was shown by compounds 4b and 4k against HeLa cell lines. The influence on cell cycle and mechanism of action of the most active compounds were examined too. Compound 4b had good antibacterial and anticancer activities, while 4k showed promising antifungal and anticancer activities.

A new class of half-sandwich ruthenium complexes containing Biginelli hybrids: anticancer and anti-SARS-CoV-2 activities.

In order to discover new dual-active agents, a series of novel Biginelli hybrids (tetrahydropyrimidines) and their ruthenium(II) complexes were synthesized. Newly synthesized compounds were characterized by IR, NMR, and X-ray techniques and investigated for their cytotoxic effect on human cancer cell lines HeLa, LS174, A549, A375, K562 and normal fibroblasts (MRC-5). For further examination of the cytotoxic mechanisms of novel complexes, two of them were chosen for analyzing their effects on the distribution of HeLa cells in the cell cycle phases. The results of the flow cytometry analysis suggest that the proportion of cells in G2/M phase was decreased following the increase of subG1 phase in all treatments. These results confirmed that cells treated with 5b and 5c were induced to undergo apoptotic death. The ruthenium complexes 5a-5d show significant inhibitory potency against SARS-CoV-2 Mpro. Therefore, molecule 5b has significance, while 5e possesses the lowest values of ΔGbind and Ki, which are comparable to cinanserin, and hydroxychloroquine. In addition, achieved results will open a new avenue in drug design for more research on the possible therapeutic applications of dual-active Biginelli-based drugs (anticancer-antiviral). Dual-active drugs based on the hybridization concept "one drug curing two diseases" could be a successful tactic in healing patients who have cancer and the virus SARS-CoV-2 at the same time.

Synthesis, Characterization, Antitumor Potential, BSA and DNA Binding Properties, and Molecular Docking Study of Some Novel 3-Hydroxy-3- Pyrrolin-2-Ones.

BACKGROUND: In order to make progress in discovering the new agents for cancer treatment with improved properties and considering the fact that 3-hydroxy-3-pyrrolin-2-ones belong to a class of biologically active compounds, we tested series of eleven novels 1,5-diaryl-4-(2- thienylcarbonyl)-3-hydroxy-3-pyrrolin-2-ones for their antitumor potential. METHODS: All novel compounds were characterized by spectral (IR, NMR, MS) and elemental analysis. All novel 3-hydroxy-3-pyrrolin-2-ones were screened for their cytotoxic activity on two cancer cell lines, SW480 and MDA-MB 231, and non-transformed fibroblasts (MRC-5). RESULTS: Compounds B8, B9, and B10 showed high cytotoxicity on SW480 cells together with good selectivity towards MRC-5 cells. It is important to empathize that the degree of selectivity of B8 and B10 was high (SI = 5.54 and 12.09, respectively). Besides, we explored the mechanisms of cytotoxicity of novel derivatives, B8, B9, and B10. The assay showed that tested derivatives induce an apoptotic type of cell death in SW480 cells, with a minor percent of necrotic cells. Additionally, to better understand the suitability of the compounds for potential use as anticancer medicaments, we studied their interactions with biomacromolecules (DNA or BSA). The results indicated that the tested compounds have a great affinity to displace EB from the EB-DNA complex through intercalation. Also, DNA and BSA molecular docking study was performed to predict the binding mode and the interaction region of the compounds. CONCLUSION: Achieved results indicate that our compounds have the potential to become candidates for use as medicaments.

Antitumor activity, DNA and BSA interactions of novel copper(II) complexes with 3,4-dihydro-2(1H)-quinoxalinones.

In order to discover new therapeutically active agents a series of novel copper(II) complexes with 3,4-dihydro-2(1H)-quinoxalinones were synthesized. All complexes were characterized by IR and EPR spectroscopic techniques and examined for their cytotoxic effect on human cancer cell lines HeLa, LS174, A549 and normal fibroblasts (MRC-5). For further examination of the cytotoxic mechanisms of novel complexes, three of them were chosen for analysing their effects on the distribution of HeLa cells in the cell cycle phases. The results of the flow cytometry analysis suggest that tested complexes lead to time-dependent accumulation of the cells in S and G2/M phases. The strongest accumulation effect showed complex 2d after 48 h of incubation. Competitive experiments with ethidium bromide (EB) indicated that tested compound 2d have affinity to displace EB from the EB-DNA complex through intercalation. Also, the binding parameters values for 2d-BSA complex showed that a reversible 2d-BSA complex is formed and ligand 2d can be stored and carried by BSA.

3D HeLa spheroids as a model for investigating the anticancer activity of Biginelli-hybrids.

In previous study, we examined the anticancer effects of novel Biginelli-hybrids against HeLa cell line on 2D monolayer culture. The five most effective compounds were chosen for further analysis of their anticancer activity against HeLa spheroids. Using the 3D models implies the possible differences in anticancer effects and mechanisms of activity of tested compounds. The compounds 4c and 4d exerted the strongest activity against 3D HeLa spheroids and induced to some extent loosened cell-cell contacts in spheroids, leading to the largest reduction in the diameter of the spheroids. Additionally, the highest accumulation of the cells in the subG1 phase of the cell cycle was observed after the treatment with compounds 4d and 4c, while the compound 4f led to the G2/M arrest. The invasion potential of treated HeLa cells in spheroids was monitored by imaging of spheroids embedded in a matrix made of matrigel and collagen and by determination of MMP2, MMP9, and VEGF gene expression levels. The compound 4l did not show invasion-suppressive activity, while the compounds 4c and 4d exerted the strongest anti-invasive activity.

2,4-Diketo esters: Crucial intermediates for drug discovery.

Convenient structures such as 2,4-diketo esters have been widely used as an effective pattern in medicinal chemistry and pharmacology for drug discovery. 2,4-Diketonate is a common scaffold that can be found in many biologically active and naturally occurring compounds. Also, many 2,4-diketo ester derivatives have been prepared due to their suitable synthesis. These synthetic drugs and natural products have shown numerous interesting biological properties with clinical potential as a cure for the broad specter of diseases. This review aims to highlight the important evidence of 2,4-diketo esters as a privileged scaffold in medicinal chemistry and pharmacology. Herein, numerous aspects of 2,4-diketo esters will be summarized, including synthesis and isolation of their derivatives, development of novel synthetic methodologies, the evaluation of their biological properties as well as the mechanisms of action of the diketo ester derivates. This paperwork is expected to be a comprehensive, trustworthy, and critical review of the 2,4-diketo ester intermediate to the chemistry community.

Chitosan nanobeads loaded with Biginelli hybrids as cell-selective toxicity systems with a homogeneous distribution of the cell cycle in cancer treatment.

Tetrahydropyrimidines are a class of azaheterocycles, also called Biginelli hybrids (obtained from the Biginelli reaction), that have attracted an enormous interest in the medicinal chemistry community in recent years, due to a broad biological activity, such as anticancer, antiviral, anti-inflammatory, antidiabetic, antituberculosis activities, etc. According to SciFinder®, more than 70 000 different Biginelli-like compounds have been covered in publications. However, although the Biginelli reaction can yield a large number of compounds with a broad range of activities, none of them have been captured in a carrier. In this study, chitosan-based (Ch) nanoparticles (NPs) containing three different molecules (Biginelli hybrids) were developed and tested for the first time as simple and promising vehicles for anticancer Biginelli-based drugs. The key features of NPs, such as size, surface morphology, drug encapsulation efficiency, and in vitro release were systematically investigated. Rather weak cell selectivity of pure Biginelli hybrids (A-C) to selected cancer cell lines has improved and this has been accompanied with two-to-four times stronger cytotoxic effect of A-C loaded Ch NPs, with a triple reduction in toxicity to healthy cells (MRC-5). It has been observed that the examined NPs induce apoptosis. The cell cycle analysis has confirmed the influence of A-loaded Ch (A-Ch), B-loaded Ch (B-Ch), and C-loaded Ch (C-Ch) on the cell cycle distribution, which was homogenously affected. This is the difference with regard to the effect of A, B, and C on the cell cycle. It has been established that the increased selectivity and antitumor activity of NPs are related to the presence of the carrier.

Synthesis, Anticancer Evaluation and Synergistic Effects with cisplatin of Novel Palladium Complexes: DNA, BSA Interactions and Molecular Docking Study.

BACKGROUND: In order to discover new agents for chemotherapy with improved properties compared to the existing agents and bearing in mind the fact that some Pd complexes possess better antitumor activity and exhibit less kidney toxicity compared to cisplatin, a series of novel square-planar palladium(II) complexes [Pd (L)2] (3a-f) with O,O bidentate ligands [L = ethyl 2- hydroxy-alkyl(aryl)-4-oxo-2-butenoate] were synthesized. METHODS: All complexes were characterized by spectral (UV-Vis, IR, NMR, ESI-MS) and X-ray analysis and examined for their cytotoxic effect on human cancer cell lines HeLa and MDA-MB 231 and normal fibroblasts (MRC-5). Fluorescence spectroscopic method was used for investigations of the interactions between CT-DNA or bovine serum albumin (BSA) and complex 3c. Viscosity measurements and molecular docking study were performed to confirm the mode of interactions between DNA and BSA and complex 3c. RESULTS: Complexes that showed the best results, 3c, 3d, and 3e, were placed under further investigations. Selected complexes induced apoptosis and cell cycle arrest in HeLa and MDA-MB 231 cells. Low concentrations of 3c and 3e showed strong to moderate synergism with low concentrations of cisplatin. The interaction of 3d with cisplatin was antagonistic in all used concentrations, but low IC50 value indicates its usefulness as a single cytotoxic agent. It was also noted that the change of viscosity is more pronounced in DNA solution after addition of complex 3c. CONCLUSION: Obtained results indicate that the novel palladium(II) complexes have the potential to become candidates for treatment in anticancer therapy.

Gal-3 Deficiency Suppresses Novosphyngobium aromaticivorans Inflammasome Activation and IL-17 Driven Autoimmune Cholangitis in Mice.

Gal-3 has the role in multiple inflammatory pathways. Multiple-hit etiology of primary biliary cholangitis (PBC) and evolving immune response at various stages of the disease includes involvement of Gal-3 in PBC pathogenesis. In this study we aimed to clarify the role of Gal-3 in Novosphingobium aromaticivorans (N. aromaticivorans) induced biliary disease. Autoimmune cholangitis was induced in mice by two intra-peritoneal injections of N. aromaticivorans within 2 weeks. The role of Gal-3 was evaluated by using Lgals3-/- mice and mice treated with Gal-3 inhibitor. The histological and serological parameters of disease, phenotype of dendritic, NK, NKT, and T cells and inflammasome expression were evaluated. Marked attenuation of the disease in Lgals3-/- and Gal-3 inhibitor, DAVANAT®, treated mice is manifested by the absence of bile duct damage, granulomas and fibrosis. Liver infiltrates of N. aromaticivorans infected wild type mice had higher incidence of pro-inflammatory macrophages, dendritic cells, NK, NKT, and T cells. Lgals3 deletion and treatment with Gal-3 inhibitor reduced inflammatory mononuclear cell infiltrate, expression of NLRP3 inflammasome in the liver infiltrates and interleukin-1ß (IL-1ß) production in the livers of N. aromaticivorans infected mice. In vitro stimulation of wild type peritoneal macrophages with N. aromaticivorans caused increased NLRP3 expression, caspase-1 activity and IL-1ß production compared with Lgals3-/- cells. Our data highlight the importance of Gal-3 in promotion of inflammation in N. aromaticivorans induced PBC by enhancing the activation of NLRP3 inflammasome and production of IL-1ß and indicate Gal-3 as possible therapeutical target in autoimmune cholangitis. Galectin-3 appears involved in inflammatory response to gut commensal leading to PBC.

Synthesis, characterization, anticancer evaluation and mechanisms of cytotoxic activity of novel 3-hydroxy-3-pyrrolin-2-ones bearing thenoyl fragment: DNA, BSA interactions and molecular docking study.

In order to make a progress in discovering a new agents for chemotherapy with improved properties and bearing in mind the fact that substituted 3-hydroxy-3-pyrrolin-2-ones belong to a class of biologically active compounds, series of novel 1,5-diaryl-4-(2-thienylcarbonyl)-3-hydroxy-3-pyrrolin-2-ones were synthesized and characterized by spectral (UV-Vis, IR, NMR, ESI-MS), X-ray and elemental analysis. All compounds were examined for their cytotoxic effect on human cancer cell lines HeLa and MDA-MB 231 and normal fibroblasts (MRC-5). Four compounds, 3-hydroxy-1-(p-tolyl)-4-(2-thienylcarbonyl)-5-(4-chlorophenyl)-2,5-dihydro-1H-pyrrol-2-one (D10), 3-hydroxy-1-(3-nitrophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D13), 3-hydroxy-1-(4-nitrophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D14), and 3-hydroxy-1-(4-chlorophenyl)-4-(2-thienylcarbonyl)-5-(4-(benzyloxy)phenyl)-2,5-dihydro-1H-pyrrol-2-one (D15), that showed the highest cytotoxicity against malignant cells and the best selectivity towards normal cells were selected for further experiments. Results obtained by investigating mechanisms of cytotoxic activity suggest that selected 3-hydroxy-3-pyrrolin-2-one derivatives in HeLa cells induce apoptosis that is associated with S phase arrest (D13, D15, and D10) or unrelated to cell cycle distribution (D14). Additionally, to better understand their suitability for potential use as anticancer medicaments we studied the interactions between biomacromolecules (DNA or BSA) and D13 and D15. The results indicated that D13 and D15 have great affinity to displace EB from the EB-DNA complex through intercalation [Ksv = (3.7 ±â€¯0.1) and (3.4 ±â€¯0.1) × 103 M-1, respectively], an intercalative mode also confirmed through viscosity measurements. Ka values, obtained as result of fluorescence titration of BSA with D13 and D15 [Ka = (4.2 ±â€¯0.2) and (2.6 ±â€¯0.2) × 105 M, respectively], support the fact that a significant amount of the tested compounds could be transported and distributed through the cells. In addition, by DNA and BSA molecular docking study for D13, D14 and D15 is determined and predicted the binding mode and the interaction region.

Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels.

In order to investigate potential therapeutically agents, novel products of Biginelli reaction (4a-l) were synthesized and exposed to cytotoxic and caspase activities, angiogenesis, cell cycle distribution, gene and microRNA expression levels, lipophilicity assessment and docking study. Among the twelve novel compounds (4a-l) evaluated for the cytotoxic activity, five of them (4c, 4d, 4f, 4k and 4l) that showed excellent activity on the tested cell lines (HeLa, LS174 and A549) were selected for further evaluation. Interestingly, compound 4f has up to three times higher selectivity index (SI) towards cancer cells than cisplatin (on HeLa, LS174 and A549 SI = 18.2, 13.5 and 11.2, respectively). The obtained results from cell cycle distribution and caspase activity indicate that tested compounds (4c, 4d, 4f, 4k and 4l) promoted caspase-9 activation, implicated in the intrinsic pathway of apoptosis. Lipophilicity of 4a-l was determinate by using reversed-phase high-performance liquid chromatography.

Biological evaluation of selected 3,4-dihydro-2(1H)-quinoxalinones and 3,4-dihydro-1,4-benzoxazin-2-ones: Molecular docking study.

In order to investigate new potential therapeutically active agents, we investigated the biological properties of two small libraries of quinoxalinones and 1,4-benzoxazin-2-ones. The results obtained showed that compounds 5, 9-11 have good cytotoxic activity against HeLa cells where the lowest IC50 value (10.46 ± 0.82 µM/mL) was measured for compound 10. Additionally, the most active compounds (5, 9-11) showed much better selectivity for MRC-5 cells (up to 17.4) compared to cisplatin. In vitro evaluation of the inhibition of the enzyme α-glucosidase showed that compounds 10 and 11 exert significant inhibition of the enzyme at 52.54 ± 0.09 and 40.09 ± 0.49 µM, respectively. Competitive experiments with ethidium bromide (EB) indicated that all tested compounds have affinity to displace EB from the EB-DNA complex through intercalation, suggesting good competition with EB (Ksv = (3.1 ± 0.2), (5.1 ± 0.1), (5.6 ± 0.2), and (6.3 ± 0.2) × 103 M-1 ). A molecular docking study was also performed to better understand the binding modes and to conclude the structure-activity relationships of the synthesized compounds.

Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper(ii) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate.

A serie of novel square pyramidal copper(ii) complexes [Cu(L)2H2O] (3a-d) with O,O-bidentate ligands [L = ethyl-2-hydroxy-4-aryl-4-oxo-2-butenoate; aryl = 3-methoxyphenyl-2a, (E)-2-phenylvinyl-2b, (E)-2-(4'-hydroxy-3'-methoxyphenyl)vinyl-2c, 3-nitrophenyl-2d, 2-thienyl-2e] were synthesized and characterized by spectral (UV-Vis, IR, ESI-MS and EPR), elemental and X-ray analysis. The antimicrobial activity was estimated by the determination of the minimal inhibitory concentration (MIC) using the broth microdilution method. The most active antibacterial compounds were 3c and 3d, while the best antifungal activity was showed by complexes 3b and 3e. The lowest MIC value (0.048 mg mL-1) was measured for 3c against Proteus mirabilis. The cytotoxic activity was tested using the MTT method on human epithelial carcinoma HeLa cells, human lung carcinoma A549 cells and human colon carcinoma LS174 cells. All complexes showed extremely better cytotoxic activity compared to cisplatin at all tested concentrations. Compound 3d expressed the best activity against all tested cell lines with IC50 values ranging from 7.45 to 7.91 µg mL-1. The type of cell death and the impact on the cell cycle for 3d and 3e were evaluated by flow cytometry. Both compounds induced apoptosis and S phase cell cycle arrest. The interactions between selected complexes (3d and 3e) and CT-DNA or bovine serum albumin (BSA) were investigated by the fluorescence spectroscopic method. Competitive experiments with ethidium bromide (EB) indicated that 3d and 3e have a propensity to displace EB from the EB-DNA complex through intercalation suggesting strong competition with EB [Ksv = (1.4 ± 0.2) and (2.9 ± 0.1) × 104 M-1, respectively]. Ksv values indicate that these complexes bind to DNA covalently and non-covalently. The achieved results in the fluorescence titration of BSA with 3d and 3e [Ka = (2.9 ± 0.2) × 106 and (2.5 ± 0.2) × 105 M, respectively] showed that the fluorescence quenching of BSA is a result of the formation of the 3d- and 3e-BSA complexes. The obtained Ka values are high enough to ensure that a significant amount of 3d and 3e gets transported and distributed through the cells.

Biological maturity status and motor performance in fourteen-year-old basketball players / Estado de madurez biológica y desempeño motriz en jugadores de baloncesto de catorce años de edad

The aims of this study were to detect biological maturity and certain athletic skills in boys aged 14 participating in competitive basketball, and to compare certain athletic skills of participants according to their biological maturity status. The participants were most talented Serbian basketball players (n= 49) who were divided into three groups according to their maturity status: early (n= 14), average (n= 24) and late maturing (n= 11). Biological maturity status of participants was assessed by technique developed by Mirwald et al. (2002). Nine tests of basic athletic skills: vertical jump, medicine ball throwing, run at 20, 30 and 50 m, agility t-test, zigzag agility drill, agility run 4x15 m, the line drill, as well as four basketball skills field tests (speed spot shooting, passing, control dribble and defensive movement) were applied. The results of this study showed that the three groups of subjects differed in applied variables (p <0.05). Average maturers achieved the best results in almost all variables, while late maturers achieved the worst results. Early maturers achieved the best results only in one variable - medicine ball throwing. Only harmonized chronological and biological age, i.e. chronological and biological growth and development, enable the best demonstration of motor abilities based on morphological characteristics.

Los objetivos fueron detectar la madurez biológica y ciertas habilidades atléticas en los varones mayores de 14 años que participan en el baloncesto competitivo, y compararlas en función de su estado de madurez biológica. La muestra se conformó con jugadores de baloncesto serbios de mayor talento (n= 49) que fueron divididos en tres grupos de acuerdo a su estado de madurez: temprana (n= 14), promedio (n= 24) y tardía (n= 11). El estado de madurez biológica de los participantes se evaluó mediante la técnica desarrollada por Mirwald et al. (2002). Se aplicaron nueve pruebas de habilidades atléticas básicas: salto vertical, lanzamiento de balón medicinal, carrera de 20, 30 y 50 m, prueba t de agilidad, agilidad en zig-zag, carrera en 4x15 m, línea de perforación, así como pruebas de campo de baloncesto de cuatro habilidades (velocidad de disparos punto, de paso, control de regate y movimiento defensivo). Los resultados de este estudio mostraron que los tres grupos de sujetos diferían en variables aplicadas (p <0,05). Los jugadores de maduración media obtuvieron los mejores resultados en casi todas las variables, mientras que los jugadores de maduración tardía alcanzaron los peores resultados. Los jugadores de maduración temprana lograron el mejor resultado en sólo una variable ­ el lanzamiento de balón medicinal. Solamente el desarrollo cronológico armónico y la edad biológica, es decir, el crecimiento y el desarrollo cronológico y biológico, permiten la mejor demostración de las habilidades motoras basadas en características morfológicas.