Biomolecular Interactions and Anticancer Mechanisms of Ru(II)-Arene Complexes of Cinnamaldehyde-Derived Thiosemicarbazone Ligands: Analysis Combining In Silico and In Vitro Approaches.

Our study focuses on synthesizing and exploring the potential of three N-(4) substituted thiosemicarbazones derived from cinnamic aldehyde, alongside their Ru(II)-(η6 -p-cymene)/(η6-benzene) complexes. The synthesized compounds were comprehensively characterized using a range of analytical techniques, including FT-IR, UV-visible spectroscopy, NMR (1H, 13C), and HRMS. We investigated their electronic and physicochemical properties via density functional theory (DFT). X-ray crystal structures validated structural differences identified by DFT. Molecular docking predicted promising bioactivities, supported by experimental observations. Notably, docking with EGFR suggested an inhibitory potential against this cancer-related protein. Spectroscopic titrations revealed significant DNA/BSA binding affinities, particularly with DNA intercalation and BSA hydrophobic interactions. RuPCAM displayed the strongest binding affinity with DNA (Kb = 6.23 × 107 M-1) and BSA (Kb = 9.75 × 105 M-1). Assessed the cytotoxicity of the complexes on cervical cancer cells (HeLa), and breast cancer cells (MCF-7 and MDA-MB 231), revealing remarkable potency. Additionally, selectivity was assessed by examining MCF-10a normal cell lines. The active complexes were found to trigger apoptosis, a vital cellular process crucial for evaluating their potential as anticancer agents utilizing staining assays and flow cytometry analysis. Intriguingly, complexation with Ru(II)-arene precursors significantly amplified the bioactivity of thiosemicarbazones, unveiling promising avenues toward the creation of powerful anticancer agents.

Design, Synthesis, and Characterization of Novel Thiazolidine-2,4-Dione-Acridine Hybrids as Antitumor Agents.

This study focuses on the synthesis and structural characterization of new compounds that integrate thiazolidine-2,4-dione, acridine moiety, and an acetamide linker, aiming to leverage the synergistic effects of these pharmacophores for enhanced therapeutic potential. The newly designed molecules were efficiently synthesized through a multi-step process and subsequently transformed into their hydrochloride salts. Comprehensive spectroscopic techniques, including nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HRMS), infrared (IR) spectroscopy, and elemental analysis, were employed to determine the molecular structures of the synthesized compounds. Biological evaluations were conducted to assess the therapeutic potential of the new compounds. The influence of these derivatives on the metabolic activity of various cancer cell lines was assessed, with IC50 values determined via MTT assays. An in-depth analysis of the structure-activity relationship (SAR) revealed intriguing insights into their cytotoxic profiles. Compounds with electron-withdrawing groups generally exhibited lower IC50 values, indicating higher potency. The presence of the methoxy group at the linking phenyl ring modulated both the potency and selectivity of the compounds. The variation in the acridine core at the nitrogen atom of the thiazolidine-2,4-dione core significantly affects the activity against cancer cell lines, with the acridin-9-yl substituent enhancing the compounds' antiproliferative activity. Furthermore, compounds in their hydrochloride salt forms demonstrated better activity against cancer cell lines compared to their free base forms. Compounds 12c·2HCl (IC50 = 5.4 ± 2.4 µM), 13d (IC50 = 4.9 ± 2.9 µM), and 12f·2HCl (IC50 = 4.98 ± 2.9 µM) demonstrated excellent activity against the HCT116 cancer cell line, and compound 7d·2HCl (IC50 = 4.55 ± 0.35 µM) demonstrated excellent activity against the HeLa cancer cell line. Notably, only a few tested compounds, including 7e·2HCl (IC50 = 11.00 ± 2.2 µM), 7f (IC50 = 11.54 ± 2.06 µM), and 7f·2HCl (IC50 = 9.82 ± 1.92 µM), showed activity against pancreatic PATU cells. This type of cancer has a very high mortality due to asymptomatic early stages, the occurrence of metastases, and frequent resistance to chemotherapy. Four derivatives, namely, 7e·2HCl, 12d·2HCl, 13c·HCl, and 13d, were tested for their interaction properties with BSA using fluorescence spectroscopic studies. The values for the quenching constant (Ksv) ranged from 9.59 × 104 to 10.74 × 104 M-1, indicating a good affinity to the BSA protein.

Exploring the binding properties of DNA/BSA and cytotoxicity studies with new terpyridine-ester-based metal complexes (M = Fe(III), Ni(II), Cu(II) and Ru(III)) - A comparative analysis.

Many terpyridines and their metal complexes are known to exhibit remarkable potential for the interaction of biological targets. Notably, a subtle change in the structure of the ligand can influence these interactions significantly. In this regard, it would be very interesting to assess the binding affinity of functionalized molecules with DNA/BSA. In this work, a novel ester-based terpyridine (L) and the corresponding four metal complexes with Ni(II) (MC1), Cu(II) (MC2), Fe(III) (MC3) and Ru(III) (MC4) were prepared and structurally characterized using various spectroscopic and analytical techniques including the validation of molecular structures of ligand (L) and Ni(II)-Tpy complex (MC1). The EPR data demonstrate that MC1 is diamagnetic and other complexes (MC2-MC4) exhibit paramagnetic behavior. Additionally, the structures of ligands and metal complexes were determined using DFT studies and the same were utilized for the docking studies. Interestingly, MC3 and MC4 exhibit a predominant lowest binding energy of -9.62 Kcal/mol (with DNA) and -10.05 Kcal/mol (with BSA) respectively. The binding affinity of the ligand and its complexes with protein and DNA was evaluated by spectroscopic techniques. Notably, the cytotoxicity studies of L and MC1-MC4 were performed against the MCF-7 (human breast cancer) cell lines. The complex MC4 displayed great activity with an IC50 of 3.5 ±â€¯1.75 µM among all synthesized compounds and comparable with cisplatin.

Hydrazone-flavonol based oxidovanadium(V) complexes: Synthesis, characterization and antihyperglycemic activity of chloro derivative in vivo.

Wet synthesis approach afforded four new heteroleptic mononuclear neutral diamagnetic oxidovanadium(V) complexes, comprising salicylaldehyde-based 2-furoic acid hydrazones and a flavonol coligand of the general composition [VO(fla)(L-ONO)]. The complexes were comprehensively characterized, including chemical analysis, conductometry, infrared, electronic, and mass spectroscopy, as well as 1D 1H and proton-decoupled 13C(1H) NMR spectroscopy, alongside extensive 2D 1H1H COSY, 1H13C HMQC, and 1H13C HMBC NMR analyses. Additionally, the quantum chemical properties of the complexes were studied using Gaussian at the B3LYP, HF, and M062X levels on the 6-31++g(d,p) basis sets. The interaction of these hydrolytically inert vanadium complexes and the BSA was investigated through spectrofluorimetric titration, synchronous fluorimetry, and FRET analysis in a temperature-dependent manner, providing valuable thermodynamic insights into van der Waals interactions and hydrogen bonding. Molecular docking was conducted to gain further understanding of the specific binding sites of the complexes to BSA. Complex 2, featuring a 5-chloro-substituted salicylaldehyde component of the hydrazone, was extensively examined for its biological activity in vivo. The effects of complex administration on biochemical and hematological parameters were evaluated in both healthy and diabetic Wistar rats, revealing antihyperglycemic activity at millimolar concentration. Furthermore, histopathological analysis and bioaccumulation studies of the complex in the brain, kidneys, and livers of healthy and diabetic rats revealed the potential for further development of vanadium(V) hydrazone complexes as antidiabetic and insulin-mimetic agents.

Organoruthenium metallocycle induced mutation in gld-1 tumor suppression gene in JK1466 strain and appreciable lifespan expansion.

Four Ru(II) complexes (A2-A5) were synthesized from the reaction of coumarin Schiff base ligands (7da2-tsc, 7da3-mtsc, 7da4-etsc and 7da5-ptsc) with [RuHCl(CO)(PPh3)3]. The compounds were characterized by FT-IR, UV-Vis, 1H, 13C and 31P NMR, mass spectrometry and crystallographic analysis. Calf Thymus DNA (CT-DNA) binding studies revealed the intercalative mode of binding of the complexes with DNA. The results of Bovine serum albumin (BSA) binding studies established the interaction between BSA followed static quenching mechanism. The cytotoxic effects of the complexes and the ligands were evaluated against breast (MCF-7 and MDA-MB-231) and lung carcinoma cell lines (A549 and NCI-H460) using MTT assay. Complex A4 demonstrated potent cytotoxic effects on both breast and lung cancer cells. Furthermore, morphological observations and FACS analysis showed the decrease in cell density by complex A4 by induced morphological changes and apoptotic body formation and cell death in both breast and lung cancer cells. Moreover, the invertebrate model Caenorhabditis elegans was employed to assess the in vivo anticancer activity of compound A4. The findings indicated that the treatment with A4 reduced tumor development and significantly extended organismal lifespan by 64 % in the tumoral strain JK1466 without adversely affecting essential physiological functions of the worm. Additionally, A4 demonstrated an upregulation of two crucial antioxidant defense genes. Overall, these results suggested that the compound A4 can be a potential candidate with novel chemotherapeutic applications.

Studies on synthesis and influence of sterically driven Ni(II)-terpyridine (NNN) complexes on BSA/DNA binding and anticancer activity.

The present work demonstrates the synthesis, structural diversity and coordination behavior of some selected new Ni(II)-Tpy complexes. The structural analysis revealed the coordination of the selected terpyridine ligands with the core metal atom in two different modes via dimeric species (1:1 fashion) through the Cl-bridging and a bis(Tpy)-Ni complex (2:1 fashion). Perhaps the most striking manifestations of these Ni(II)-Tpy complexes are BSA/DNA binding ability and anticancer activity. In addition, the cytotoxicity studies of Tpy ligand (4-([2,2':6',2″-terpyridin]-4'-yl)phenyl 5-methylthiophene-2-carboxylate) and the Ni(II) complexes were carried out using lung cancer cell line (A549), breast cancer cell line (MCF-7) and normal cell line (Vero cell). The cytotoxicity results were compared with the cisplatin control group. Notably, bis-terpyridyl complex 3C (R = 4-([2,2':6',2″-terpyridin]-4'-yl)phenyl 4-isopropoxybenzoate) demonstrates better activity with the IC50 value of 23.13 ± 3 µm for A549 and 22.7 ± 3 for MCF-7. The DFT calculations reveal the significant energy differences of HOMO and LUMO for the ligands and their corresponding Ni(II) complexes. The Tpy ligands and Ni(II)-Tpy complexes were investigated for BSA binding and further all the Ni(II) complexes were analyzed for DNA binding studies.

Binuclear palladacycles with ionisable and non-ionisable tethers as anticancer agents.

The search for novel anticancer agents to replace the current platinum-based treatments remains an ongoing process. Palladacycles have shown excellent promise as demonstrated by our previous work which yielded BTC2, a binuclear palladadycle with a non-ionisable polyethylene glycol (PEG) tether. Here, we explore the importance of the PEG-tether length on the anticancer activity of the binuclear palladacycles by comparing three analogous binuclear palladacycles, BTC2, BTC5 and BTC6, in the oestrogen receptor positive MCF7 and triple-negative MDA-MB-231 breast cancer cell lines. In addition, these are compared to another analogue with an ionisable morpholine tether, BTC7. Potent anticancer activity was revealed through cell viability studies (MTT assays) revealed that while BTC6 showed similar potent anticancer activity as BTC2, it was less toxic towards non-cancerous cell lines. Interestingly, BTC7 and BTCF were less potent than the PEGylated palladacycles but showed significantly improved selectivity towards the triple-negative breast cancer cells. Cell death analysis showed that BTC7 and BTCF significantly induced apoptosis in both the cancer cell lines while the PEGylated complexes induced both apoptosis and secondary necrosis. Furthermore, experimental and computational DNA binding studies indicated partial intercalation and groove binding as the modes of action for the PEGylated palladacycles. Similarly, experimental and computational BSA binding studies indicated and specific binding sites in BSA dependent on the nature of the tethers on the complexes.

Synthesis, characterization, and BSA binding studies of newfangled 2-phenylacetohydrazide derivatives.

Five 2-phenylacetohydrazide derivatives (BPAH = N'-benzylidene-2-phenylacetohydrazide, HBPAH = N'-(2-hydroxybenzylidene)-2-phenylacetohydrazide), PPAH = 2-phenyl-N'-3-phenylallylideneacetohydrazide, FMPAH = N'-(furan-2-ylmethylene)-2-phenylaceto hydrazide and EPAH = N'-ethylidene-2-phenylacetohydrazide were synthesized by the condensation of 2-phenylacetohydrazide with the corresponding aldehyde. The synthesized compounds were characterized by FTIR, 1D, and 2D NMR spectroscopy. The structure of the BPAH and PPAH were analyzed by single crystal X-ray diffraction analysis and in both crystallized compounds, the molecules adopted trans geometry around the -C[bond, double bond]N- (imine) functional group. To explore the pharmacological significance of these compounds, the binding ability of these compounds with Bovine Serum Albumin (BSA) was investigated using fluorescence spectroscopy. BPAH and PPAH showed the highest binding ability while EPAH, HBPAH, and FMPAH had lower binding ability to BSA molecules. Thermodynamic parameters ΔG, ΔH°, and ΔS° demonstrated that interactions of BSA with compounds BPAH, EPAH, FMAH, and HBPAH were exothermic while for PPAH it was endothermic. The negative enthalpy and entropy of the compounds BPAH, EPAH, FMAH, and HBPAH indicated that van der Waals' forces and hydrogen bonding played a major role in stabilizing the BSA binding with the molecules. Hydrophobic interactions were predominant in the binding of PPAH with BSA tends to interact with two sets of BSA binding sites with an increase in temperature.

Anticancer behaviour of 2,2'-(pyridin-2-ylmethylene)bis(5,5-dimethylcyclohexane-1,3-dione)-based palladium(II) complex and its DNA, BSA binding propensity and DFT study.

Herein, we report the synthesis and biological evaluation of [Pd(L)(OH2)Cl] complex (where L = 2,2'-(pyridin-2-ylmethylene)bis(5,5-dimethylcyclohexane-1,3-dione) as a novel promising anticancer candidate. The complex was characterized by single-crystal X-ray diffraction and other various spectroscopic techniques. Besides, the optimized structure was determined through DFT calculations revealing that the coordination geometry of [Pd(L)(OH2)Cl] complex is square planar. The binding propensity of [Pd(L)(OH2)Cl] complex with DNA and BSA was assessed by the spectrophotometric method. The antimicrobial profile of the ligand and its [Pd(L)(OH2)Cl] complex was screened against clinically important bacterial strains. [Pd(L)(OH2)Cl] complex showed promising activity against these microorganisms. Pd(L)(OH2)Cl] complex exhibited a potent antiproliferative potential compared to its ligand against different human cancer cells (A549, HCT116, MDA-MB-231, and HepG2) with less toxic effect against normal cells (WI-38). Additionally, [Pd(L)(OH2)Cl] complex exerted its anticancer effects against the most responsive cells (HCT116 cells; IC50 = 11 ± 1 µM) through suppressing their colony-forming capabilities and triggering apoptosis and cell cycle arrest at S phase. Quantitative PCR analysis revealed a remarkable upregulation of the mRNA expression level of p53 and caspase-3 by 4.8- and 5.9-fold, respectively, relative to control. Remarkable binding properties and non-covalent interactions between L and its [Pd(L)(OH2)Cl] complex with the binding sites of different receptors including CDK2, MurE ligase, DNA, and BSA were established using molecular docking. Based on our results, [Pd(L)(OH2)Cl] complex is an intriguing candidate for future investigations as a potential anticancer drug for the treatment of colon cancer.

A phenanthroline-based erbium (III) complex: molecular docking, DNA/BSA -binding and biological evaluation.

With the help of both theoretical as well as experimental research, in vitro binding research with CT-DNA (calf thymus) and BSA (bovine serum albumin) were carefully examined to figure out the chemotherapeutic and pharmacokinetic facets of the Erbium complex, which contains 1,10-phenanthroline (Phen). The binding characteristics and the mechanism of complex's interaction with DNA as well as the protein were determined utilizing fluorescence quenching method. Findings indicated that the complex's interaction with DNA via groove binding into DNA's minor grooves, with their binding constants falling within the 104 M-1 range. Furthermore, thermodynamic characteristics and the fluorescence emission of the tryptophan residues of the protein were obtained through fluorescence quenching studies at different temperatures. According to the results of the binding constants, the protein's interactions with the Er- complex were moderate, demonstrating that the compound may be transported effectively by the protein. Molecular docking results supported that of the experimental research. The HeLa and MCF-7 cancer cell lines, along with the normal human fibroblast cell line, were used in an MTT assay evaluation of the Er-complex cytotoxicity. The Er-complex displayed a selective inhibitory effect on the proliferation of different cancer cells.Communicated by Ramaswamy H. Sarma.

Aminoquinoline-based Re(I) tricarbonyl complexes: Insights into their antiproliferative activity and mechanisms of action.

In an effort to develop new potent anticancer agents, two Schiff base rhenium(I) tricarbonyl complexes, containing the ubiquitous aminoquinoline scaffold, were synthesized. Both aminoquinoline ligands and Re(I) complexes showed adequate stability over a 48-h incubation period. Furthermore, the cytotoxic activity of the precursor ligands and rhenium(I) complexes were evaluated against the hormone-dependent MCF-7 and hormone-independent triple negative MDA-MB-231 breast cancer cell lines. Inclusion of the [Re(CO)3Cl]+ entity significantly enhanced the cytotoxicity of the aminoquinoline Schiff base ligands against the tested cancer cell lines. Remarkably, the incorporation of the Schiff-base iminoquinolyl entity notably enhanced the cytotoxic activity of the Re(I) complexes, in comparison with the iminopyridyl entity. Notably, the quinolyl-substituted complex showed up to three-fold higher activity than cisplatin against breast cancer cell lines, underpinning the significance of the quinoline pharmacophore in rational drug design. In addition, the most active Re(I) complex showed better selectivity towards the breast cancer cells over non-tumorigenic FG-0 cells. Western blotting revealed that the complexes increased levels of γH2AX, a key DNA damage response protein. Moreover, apoptosis was confirmed in both cell lines due to the detection of cleaved PARP. The complexes show favourable binding affinities towards both calf thymus DNA (CT-DNA), and bovine serum albumin (BSA), and the order of their interactions align with their cytotoxic effects. The in silico molecular simulations of the complexes were also performed with CT-DNA and BSA targets.

Characterization, modes of interactions with DNA/BSA biomolecules and anti-tumor activity of newly synthesized dinuclear platinum(II) complexes with pyridazine bridging ligand.

Platinum-based drugs are widely recognized efficient anti-tumor agents, but faced with multiple undesirable effects. Here, four dinuclear platinum(II) complexes, [{Pt(1,2-pn)Cl}2(µ-pydz)]Cl2 (C1), [{Pt(ibn)Cl}2(µ-pydz)]Cl2 (C2), [{Pt(1,3-pn)Cl}2(µ-pydz)]Cl2 (C3) and [{Pt(1,3-pnd)Cl}2(µ-pydz)]Cl2 (C4), were designed (pydz is pyridazine, 1,2-pn is ( ±)-1,2-propylenediamine, ibn is 1,2-diamino-2-methylpropane, 1,3-pn is 1,3-propylenediamine, and 1,3-pnd is 1,3-pentanediamine). Interactions and binding ability of C1-C4 complexes with calf thymus DNA (CT-DNA) has been monitored by viscosity measurements, UV-Vis, fluorescence emission spectroscopy and molecular docking. Binding affinities of C1-C4 complexes to the bovine serum albumin (BSA) has been monitored by fluorescence emission spectroscopy. The tested complexes exhibit variable cytotoxicity toward different mouse and human tumor cell lines. C2 shows the most potent cytotoxicity, especially against mouse (4T1) and human (MDA-MD468) breast cancer cells in the dose- and time-dependent manner. C2 induces 4T1 and MDA-MD468 cells apoptosis, further documented by the accumulation of cells at sub-G1 phase of cell cycle and increase of executive caspase 3 and caspase 9 levels in 4T1 cells. C2 exhibits anti-proliferative effect through the reduction of cyclin D3 and cyclin E expression and elevation of inhibitor p27 level. Also, C2 downregulates c-Myc and phosphorylated AKT, oncogenes involved in the control of tumor cell proliferation and death. In order to measure the amount of platinum(II) complexes taken up by the cells, the cellular platinum content were quantified. However, C2 failed to inhibit mouse breast cancer growth in vivo. Chemical modifications of tested platinum(II) complexes might be a valuable approach for the improvement of their anti-tumor activity, especially effects in vivo.

In Vitro Insight on Antifungal-Specific Potentiality of Ni(II) Complex against Colletotrichum siamense and Fusarium equisetum Phytopathogens.

In an initiation to investigate a prospective bioactive compound, a mononuclear Ni(II) complex with N, N, and O donor Schiff base ligand was synthesized and characterized in the present study through FTIR, ESI-mass, and X-ray crystallographic diffraction studies. A slightly distorted octahedral geometry has been obtained for the Ni(II) complex from X-ray crystallographic diffraction studies. In vitro comprehensive biological studies show the antifungal specific efficiency of the complex against Colletotrichum siamense (AP1) and Fusarium equisetum (F.E.) pathogens, which are responsible for anthracnose and wilt disease, respectively, but no inhibitory effect on both Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration (MIC) for these pathogens was observed to be 0.25 and 0.5 mM, respectively. The experiment also reveals that significant damage of mycelia and enlarged, misshaped damaged spores are noticed in comparison to hexaconazole, used as a positive control under a light microscope post 48 h treatment of AP1 and F.E. with the MIC of the complex. The binding interaction studies of the complex with DNA and BSA performed through a variety of spectroscopic techniques demonstrate a strong binding behavior of the complex for both the binding systems. The observed negative ΔH° and ΔS° values for DNA reveal the existence of hydrogen-bonding/van der Waals interactions for DNA which was also exemplified from the molecular docking and self-assembly studies of the complex. The positive ΔH° and ΔS° values for BSA demonstrate the hydrophobic interactions of the complex with BSA. However, cytotoxicity studies against the MDA-MB-231 breast cancer cell line did not demonstrate any significant potentiality of the complex as an anticancer agent. All the bio-experimental studies provide clear evidence that the synthesized Ni(II) complex exhibits potential antifungal activity and could be used as a therapeutic fungicide agent in comparison to hexaconazole in agricultural practices.

Experimental and theoretical investigations of Erbium complex: DNA/BSA interaction, anticancer and antibacterial studies.

To assess the biological potential of an Er complex that contains a 2,2'-bipyridine ligand, various techniques such as multispectral and molecular modeling procedures were utilized to examine its DNA-binding ability, BSA binding affinity, antimicrobial effects, and anticancer properties. By analyzing fluorescent information and employing the vant' Hoff equation, important parameters such as the innate docking coefficient (Kb), Stern-Volmer coefficient (KSV), and thermodynamic properties including modifications in liberated energy (ΔG°), enthalpy (∆H°), and entropy (∆S°) were determined. The trial findings suggest that the compound can bind to DNA, primarily through groove binding. Additionally, the engagement between the Er compound and the protein BSA was examined using emission spectroscopy technique, revealing a powerful binding affinity between the compound and BSA. The Er complex binds to BSA primarily via hydrogen links and van der Waals forces, as indicated by the adverse values of ΔH° and ∆S°. Through a static quenching process, the complex significantly reduces the intrinsic fluorescence of BSA. Molecular binding calculations and rivalrous binding trials confirm that this compound dock to hydrophobic remains found in site III of BSA. Additionally, the Er complex demonstrates promising results in terms of its anticancer and antimicrobial activities based on screening tests.

In vitro BSA-binding, antimicrobial, and antitumor activity against human cancer cell lines of two lanthanide (III) complexes.

The investigation involved examining the binding of two lanthanide complexes, specifically those containing Holmium (Ho) and Dysprosium (Dy), with a ligand called 1, 10-phenanthroline (phen), and bovine serum albumin (BSA). The evaluation was carried out utilizing fluorescence measurements, Förster theory, and docking studies. The findings indicated that both the Ho-complex and Dy-complex possessed a significant ability to quench the emission of the protein. Furthermore, the primary mechanism of interaction was identified as a static process. The Kb values indicate a strong tendency of these complexes for binding with BSA. The Kb values show the strangely high affinity of BSA to complexes and the following order for binding affinity: Ho-complex > Dy-complex. The thermodynamic parameters were found to be negative, affirming that the main forces driving the interaction between BSA and the lanthanide complexes are van der Waals engagement and hydrogen bonds. Additionally, the investigation included the examination of competition site markers, and molecular docking proposed that the engagement sites of the Ho-complex and Dy-complex with BSA were predominantly located in site 3 (specifically, subdomain IB). Moreover, the Ho-complex and Dy-complex were specifically chosen for their potential anticancer and antimicrobial properties. Consequently, these complexes could present promising prospects as novel candidates for anti-tumor and antibacterial applications.

Ga(III) pyridinecarboxylate complexes: potential analogues of the second generation of therapeutic Ga(III) complexes?

A series of novel Ga(III)-pyridine carboxylates ([Ga(Pic)3]·H2O (GaPic; HPic = picolinic acid), H3O[Ga(Dpic)2]·H2O (GaDpic; H2Dpic = dipicolinic acid), [Ga(Chel)(H2O)(OH)]2·4H2O (GaChel; H2Chel = chelidamic acid) and [Ga(Cldpic)(H2O)(OH)]2 (GaCldpic; H2Cldpic = 4-chlorodipicolinic acid)) have been synthesized by simple one-step procedure. Vibrational spectroscopy (mid-IR), elemental analysis, thermogravimetric analysis and X-ray diffraction confirmed complexes molecular structure, inter and intramolecular interactions and their influence to spectral and thermal properties. Moreover, complex species speciation was described in Ga(III)-HPic and Ga(III)-H2Dpic systems by potentiometry and 1H NMR spectroscopy and mononuclear complex species were determined; [Ga(Pic)2]+ (logß021 = 16.23(6)), [Ga(Pic)3] (logß031 = 20.86(2)), [Ga(Dpic)2]- (logß021 = 15.42(9)) and [Ga(Dpic)2(OH)]2- (logß-121 = 11.08(4)). To confirm the complexes stability in 1% DMSO (primary solvent for biological testing), timescale 1H NMR spectra were measured (immediately after dissolution up to 96 h). Antimicrobial activity evaluated by IC50 (0.05 mM) is significant for GaDpic and GaCldpic against difficult to treat and multi-resistant P. aeruginosa. On the other hand, the GaPic complex is most effective against Jurkat, MDA-MB-231 and A2058 cancer cell lines and significantly also decreases the HepG2 cancer cells viability at 75 and 100 µM concentrations in a relatively short time (up to 48 h). In addition, fluorescence measurements have been used to elucidate bovine serum albumin binding activity between ligands, Ga(III) complexes and bovine serum albumin.

In vitro assessment of the antioxidative, toxicological and antimicrobial properties of battery of parabens.

The aim of this study was to evaluate antioxidative features using 2,2-diphenyl-1-pycrylhydrazyl free radical (DPPH•) scavenging method, bovine serum albumin (BSA)-binding properties with usage of spectrofluorimetric method, proliferative and cyto/genotoxic status by use of chromosome aberration test, and antimicrobial potential using broth microdilution method, followed by resazurin assay of benzyl-, isopropyl-, isobutyl and phenylparaben in vitro. Our results showed that all parabens had significant antiradical scavenger activity compared to p-hydroxybenzoic acid (PHBA) precursor. Higher mitotic index for benzyl-, isopropyl and isobutylparaben (250 µg/mL) in comparison with control was demonstrated. An increase in the frequency of acentric fragments in lymphocytes treated with benzylparaben and isopropylparaben (125 and 250 µg/mL), and isobutylparaben (250 µg/mL) was observed. Isobutylparaben (250 µg/mL) induced higher number of dicentric chromosomes. An increased number of minute fragments in lymphocytes exposed to benzylparaben (125 and 250 µg/mL) was found. A significant difference in the frequency of chromosome pulverization, between phenylparaben (250 µg/mL) and control, was detected. Benzylparaben (250 µg/mL) and phenylparaben (62.5 µg/mL) caused an increase in the number of apoptotic cells, while isopropylparaben (62.5, 125 and 250 µg/mL) and isobutylparaben (62.5 and 125 µg/mL) induced higher frequency of necrosis. Minimum inhibitory concentration (MIC) of tested parabens ranged 15.62-250 µg/mL for bacteria, and 125-500 µg/mL for the yeast. Minimum microbiocidal concentration ranged 31.25 to 500 µg/mL, and 250 to 1000 µg/mL in bacteria and fungi respectively. The lowest MICs for bacteria were observed for phenyl- (15.62 µg/mL) and isopropylparaben (31.25 µg/mL) against Enterococcus faecalis.

Electronic and ring size effects of N-heterocyclic carbenes on the kinetics of ligand substitution reactions and DNA/protein interactions of their palladium(II) complexes.

The synthesis, substitution kinetics and DNA/BSA interactions of four cationic Pd(II) complexes [Pd(1)Cl]BF4 (Pd1), [Pd(2)Cl]BF4 (Pd2), [Pd(3)Cl]BF4 (Pd3) and [Pd(4)Cl]BF4 (Pd4), derived from the reaction of [PdCl2(NCCH3)2] with ligands 2,6-bis(3-methylimidazolium-1-yl)pyridine dibromide (1), 2,6-bis(3-ethylimidazolium-1-yl)pyridine dibromide (2), 2,6-bis(1-methylimidazole-2-thione)pyridine (3), and 2,6-bis(1-ethylimidazole-2-thione)pyridine (4), respectively are reported. The complexes were characterised by various spectroscopic techniques and single crystal X-ray diffraction for compound Pd2. Kinetic reactivity of the complexes with the biologically relevant nucleophiles thiourea (Tu), L-methionine (L-Met) and guanosine 5'-monophosphate sodium salt (5'-GMP) was in the order: Pd1 > Pd2 > Pd3 > Pd4, which was largely dependent on the electronic and ring size of the chelate ligands, consistent with Density functional theory (DFT) simulations. The interactions of the complexes with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) binding titrations showed strong binding. Both the experimental and in silico data reveal CT-DNA intercalative binding mode.

Synthesis of water-soluble novel bioactive pyridine-based azo coumarin derivative and competitive cytotoxicity, DNA binding, BSA binding study, and in silico analysis with coumarin.

The diazo coupliling reaction of 3- amino pyridine with coumarin in water medium produces water soluble 6-[3-pyridyl]azocoumarin. The synthesised compound has been fully charecterised by IR, NMR, and Mass spectroscopy. The frontier molecular orbital calculations reveal that 6-[3-pyridyl]azocoumarin is more biologically and chemically active in comparison to coumarin. The cytotoxicity evaluation confirms that 6-[3-pyridyl]azocoumarin is more active than coumarin against human brain glioblastoma cell lines, LN-229 with IC50 value 9.09 µM (IC50 value for coumarin is 9.9 µM). The compound (I) has been synthesized by coupling of diazotized solution of 3-aminopyridine with coumarin in an aqueous medium at âˆ¼ pH 10. The structure of the compound (I) has been characterized using UV-vis, IR, NMR, and Mass spectral studies. Frontier molecular orbital calculations reveal that 6-[3-pyridyl]azocoumarin (I) is more active chemically and biologically in comparison to coumarin. IC50 value 9.09 and 9.9 µM of 6-[3-pyridyl]azocoumarin and coumarin respectively obtained in cytotoxicity evaluation confirms the enhanced activity of the synthesized compound against human brain glioblastoma cell lines, LN-229. The synthesized compound also shows strong binding interactions with DNA and BSA in comparison with coumarin. The DNA binding study shows groove binding interaction of the synthesized compound with CT-DNA. The nature of interaction, binding parameters and structural variations of BSA in the presence of the synthesized compound and coumarin have been evaluated using several usefull spectroscopy approaches such as UV -Vis, time resolved and stady state flurescence. The molecular docking interaction has been carried out to justify the experimental binding interaction with DNA and BSA.

The synthesis of novel water-soluble zinc (II) phthalocyanine based photosensitizers and exploring of photodynamic therapy activities on the PC3 cancer cell line.

In this study, Schiff base substituted phthalocyanine complexes (Zn1c, Zn2c) and their quaternized derivatives (Q-Zn1c, Q-Zn2c) were synthesized for the first time. Their structures have been characterized by FT-IR, 1H-NMR, UV-Vis, mass spectrometry and elemental analysis as well as. The photophysicochemical properties (fluorescence, singlet oxygen and photodegradation quantum yield) of these novel complexes were investigated in dimethylsulfoxide (DMSO) for both non-ionic and quaternized cationic phthalocyanine complexes and in aqueous solution for quaternized cationic phthalocyanine complexes. Water soluble cationic phthalocyanine compounds gave good singlet oxygen quantum yield (0.65 for Q-Zn1c, 0.66 for Q-Zn2c in DMSO; 0.65 for Q-Zn2c in aqueous solution). The binding of Q-Zn1c and Q-Zn2c to BSA/DNA was studied by using UV-Vis and fluorescence spectroscopy and these. Studies indicate that the mechanism of BSA quenching by quaternized zinc(II) phthalocyanines was static quenching. Quaternized zinc(II) phthalocyanines interacted with ct-DNA by intercalation. Quaternized zinc(II) phthalocyanines caused a decrease in cell viability and triggered apoptotic cell death after PDT was applied at a concentration that did not have a toxic effect on their own. Q-Zn1c and Q-Zn2c mediated PDT reduced the activity of SOD, CAT, GSH while increased MDA level in the prostate cancer cells. Furthermore, expression of apoptotic proteins after PDT was examined. The results revealed that the synthesized water soluble quaternized zinc(II) phthalocyanine complexes (Q-Zn1c and Q-Zn2c) are promising potential photosensitizers for PDT.