Due to their promising effects, gold(III) complexes recently drew increasing attention in the design of new metal-based anticancer therapeutics. Two gold(III) complexes, square-planar Au(DPP)Cl2+ - ...Complex 1 and distorted square-pyramidal Au(DMP)Cl3 - Complex 2 (where DPP=4,7-diphenyl-1,10-phenanthroline and DMP=2,9-dimethyl-1,10-phenanthroline) were previously synthetized, described and approved as complexes with pronounced cytotoxic effects on colorectal HCT-116 and breast MDA-MB-231 cancer cells. This study investigated the type of cell death by AO/EB double staining, and identification of possible targets responsible for their cytotoxicity, monitored by immunofluorescence and qPCR methods. Both complexes induced apoptosis in all applied concentrations. In the HCT-116 cells apoptosis was activated by external apoptotic pathway, via increase of Fas receptor protein expression and Caspase 8 gene expression. Also, the mitochondrial pathway was triggered by affecting the Bcl-2 members of regulatory proteins and increased caspase 9 protein expression. In MDA-MB-231 cells, apoptosis was initiated from the mitochondria, due to disbalance between expressions of pro- and anti-apoptotic Bcl-2 family members and caspase 9 activation. Complex 1 shows better activity compared to Complex 2, which is in accordance with its structural characteristics. The results deal weighty data about proapoptotic activity of gold(III) complexes and highlighted potential targets for cancer therapy.
The kinetics of the substitution reactions between bifunctional Au(III) complexes, AuCl
2
(bipy)
+
, AuCl
2
(dach)
+
and AuCl
2
(en)
+
(bipy = 2,2″-bipyridine, dach = (1 ...R,2R)-1,2-diaminocyclohexane, en = ethylenediamine), with biologically relevant ligands such as glutathione (GSH), L-methionine (L-Met) and L-cysteine (L-Cys) is determined. All kinetic studies are performed in 25 mM Hepes buffer (pH = 7.2) in the presence of NaCl (25 mM) to prevent hydrolysis of the complexes. The reactions were followed under pseudo-first-order conditions using stopped-flow UV-Vis spectrophotometry at determined working wavelengths at three different temperatures (288.2, 298.1, and 309.8 K). DFT theoretical approach was applied to calculate thermodynamic and kinetic parameters that determined an operative mechanism of substitution reactions for all complexes and L-Cys as a selected model substituent. The obtained kinetic data showed that all complexes have similar reactivity; AuCl
2
(bipy)
+
is the most reactive while AuCl
2
(en)
+
is the least reactive. The second step of the substitution reaction is much faster than the first. The reactivity of the studied nucleophiles decreases in order L-Met > L-Cys > GSH. According to the values of the activation parameters determined experimentally and theoretically, all substitutions follow an associative model.
•The 3-(1-m-chloridoethylidene)-chromane-2,4‑dione was characterized by x-ray structural analysis.•The 3-(1-m-chloridoethylidene)-chromane-2,4‑dione was characterized by spectroscopic and DFT ...methods.•The hirshfeld surface analysis of 3-(1-m-chloridoethylidene)-chromane-2,4‑dione was performed.•The electronic structure of 3-(1-m-chloridoethylidene)-chromane-2,4‑dione was examined using a quantum chemical approach.•The inhibitory nature of 3-(1-m-chloridoethylidene)-chromane-2,4‑dione against the adenosine A2A (ADORA2A) receptor was investigated by molecular docking and dynamics.
The coumarin derivative, 3-(1-m-chloridoethylidene)-chroman-2,4‑dione, was previously synthesized by a conventional method. Detailed structural characterization of the obtained compound was performed by using X-ray crystallography and vibrational analysis. Experimental data were confirmed by the optimization of a structure employing three common functionals (B3LYP-D3BJ, M06–2X, and APF-D) in combination with a 6–311+G(d,p) basis set. Low values of the average absolute error and the high values of the correlation coefficient for bond lengths and angles, proved that B3LYP-D3BJ could be used for the structural and spectral analysis. The stability of the investigated compound was determined by Fukui functions, NBO, and QTAIM analyses along with various reactivity parameters. The special emphasis in the discussion was put on the role of a chlorine atom for the overall stability and reactivity by comparison with 3-(1-(phenylamino)ethylidene)-chromane-2,4‑dione. In silico simulations with Adenosine A2a receptors (ADORA2A), were performed using molecular docking and dynamics methods for both coumarin derivatives. The thermodynamic parameters and specific interactions proved the importance of chlorine atom for possible biological activity.
This aimed to develop a comprehensive theoretical protocol for examining substitution reaction processes. The researchers used a theoretical quantum-mechanical protocol based on the QM-ORSA approach, ...which estimates the kinetic parameters of thermodynamically favourable reaction pathways. This theoretical protocol was validated by experimentally investigating substitution mechanisms in two previously synthesised Pd(II) complexes:
-(3-(1-(2-hydroxypropylamino)ethylidene)chroman-2,4-dione)palladium(II) (C1) and
-(3-(1-(2-mercaptoethylamino)-ethylidene)-chroman-2,4dione)palladium(II) (C2), along with biologically relevant nucleophiles, namely L-cysteine (l-Cys), L-methionine (l-Met), and guanosine-5'-monophosphate (5'-GMP). Reactions were investigated under pseudo-first-order conditions, monitoring nucleophile concentration and temperature changes using stopped-flow UV-vis spectrophotometry. All reactions were conducted under physiological conditions (pH = 7.2) at 37 °C. The reactivity of the studied nucleophiles follows the order: l-Cys > l-Met > 5'-GMP, and the reaction mechanism is associative based on the activation parameters. The experimental and theoretical data showed that C2 is more reactive than C1, confirming that the complexes' structural and electronic properties greatly affect their reactivity with selected nucleophiles. The study's findings have confirmed that the primary interaction occurs with the acid-base species L-Cys, mostly through the involvement of the partially negative sulfur atom (87.2%). On the other hand, C2 has a higher propensity for reacting with L-Cys
, primarily through the partially negative oxygen atom (92.6%). The implementation of this theoretical framework will significantly restrict the utilization of chemical substances, hence facilitating cost reduction and environmental protection.
In this work we synthesized new monofunctional gold(III) complex Au(Cl‐Ph‐tpy)ClCl2 (Cl‐Ph‐tpy = 4′‐4‐chlorophenyl‐2,2′:6′, 2″‐terpyridine). This complex was characterized by UV–Vis, NMR, IR, and ...ESI‐MS spectrometry. The kinetic study of the substitution reactions of the Au‐Cl‐Ph‐tpy complex with biomolecules showed that the rate constants depend on the nature of the entering nucleophile. Based on the calculated values of entropy (∆H≠ > 0) and enthalpy (∆S≠ < 0) the proposed substitution mechanism is associative. Additionally, the relative stability and thermodynamic properties of Au‐Cl‐Ph‐tpy complex were compared with the analogue Au‐tpy complex by the B3LYP/def2‐svp method. DNA/BSA binding studies showed that Au‐Cl‐Ph‐tpy complex interacts with CT DNA through the intercalation and moderately quenches the fluorescence of tryptophan residues in serum albumin (BSA). Molecular docking confirmed results obtained by spectroscopic experiments and suggested site I (subdomain IIA) for binding of Au complex to BSA. We demonstrated that the Au chlorophenyl terpyridine complex possessed significant in vitro cytotoxic activity against human oral squamous carcinoma cells (CAL‐27), induced apoptosis, inhibited proliferation of CAL‐27 cells, and induced cell cycle disturbance. Treatment of CAL‐27 cells with the Au complex enhanced expression of cyclin‐dependent kinase inhibitors p21 and p27, resulting in cell cycle arrest in the G1 phase, reduced the percentage of CAL‐27 cells in S phase and decreased expression of Ki‐67. Additionally, Au complex reduced expression of phosphorylated STAT3 and downstream regulated molecules associated with cancer stemness, NANOG, and Sox2 protein.
We demonstrated that Au chlorophenyl terpyridine complex possess significant in vitro cytotoxic activity against human oral squamous carcinoma cells (CAL‐27), induced apoptosis, inhibited proliferation of CAL‐27 cells, and induced cell cycle disturbance.
This research explores the synthesis, characterization, and biological activities of silver nanoparticles (AgNPs) derived from acetone (AgNPs-acetone) and aqueous (AgNPs-H
O) extracts of
. The ...nanoparticles exhibit isometric morphology and uniform size distribution, as elucidated through Transmission Electron Microscopy (TEM) and high-resolution TEM (HRTEM) analyses. The utilization of Scanning Transmission Microscopy (STEM) with High-Angle Annular Dark-Field (HAADF) imaging and energy dispersive spectrometry (EDS) confirms the crystalline nature of AgNPs. Fourier Transform Infrared (FTIR) analysis reveals identical functional groups in the plant extracts and their corresponding AgNPs, suggesting the involvement of phytochemicals in the reduction of silver ions. Spectrophotometric monitoring of the synthesis process, influenced by various parameters, provides insights into the kinetics and optimal conditions for AgNP formation. The antioxidant activities of the plant extracts and synthesized AgNPs are evaluated through DPPH and ABTS methods, highlighting AgNPs-acetone as a potent antioxidant. Third-instar larvae exposed to the extracts have differential effects on DNA damage, with the acetone extract demonstrating antigenotoxic properties. Similarly, biosynthesized AgNPs-acetone displays antigenotoxic effects against EMS-induced DNA damage. The genotoxic effect of water extract and AgNPs-acetone was dose-dependent. Hemolytic potential is assessed on rat erythrocytes, revealing that low concentrations of AgNPs-acetone and AgNPs-H
O had a nontoxic effect on erythrocytes. Cytotoxicity assays demonstrate time-dependent and dose-dependent effects, with AgNPs-acetone exhibiting superior cytotoxicity. Proapoptotic activity is confirmed through apoptosis induction, emphasizing the potential therapeutic applications of AgNPs. The antimicrobial activity of AgNPs reveals concentration-dependent effects. AgNPs-H
O display better antibacterial activity, while antifungal activities are comparable between the two nanoparticle types.
In this research study, silver nitrate and an aqueous extract of the Agrimonia eupatoria L. plant were used for the synthesis of silver nanoparticles (AgNPs). The optimal conditions for this green ...synthesis were examined: the concentration of starting substances, pH value, and temperature. For the maximum AgNP yield, the best conditions were a 5 mM AgNO3 concentration, 1% extract concentration, a temperature of 25 °C, pH = 6, and a 3 h reaction time.
At the end of the last century, it was revealed that quinones with one, two, and three aromatic rings could inhibit HIV-1 protease, an enzyme crucial for HIV (Human Immunodeficiency Virus) ...replication. Since HIV-1 protease acts as key target for AIDS (Acquired Immunodeficiency Syndrome) medications, the development of efficient inhibitor of this protein would lead to an increase in medical treatment and a decrease in the drug resistance. Later research revealed that hydroxyquinones can block HIV-1 protease at the micromolar level, which enabled a direction for the creation of HIV medications. Anthrarufin (1,5-dihydroxy-9,10-anthraquinone) is an anthraquinone that possesses a moderate antioxidative capacity and antimalaric activity. In this study, molecular docking simulations were used to examine the molecular interactions between anthrarufin, its monoanion and dianion as ligands, and HIV-1 reverse transcriptase (HIV-1 RT) as a target protein. Using AGFR software, the binding site of the HIV-1 RT was identified. The three-dimensional crystal structure of HIV-1 RT was downloaded from the Protein Data Bank (PDB ID: 2ZD1). Dolutegravir, nevirapine, anthrarufin, anthrarufin-anion and anthrarufin-dianion are used as ligands in the molecular docking simulations together with rilpivirine (TMC278), a non-nucleoside inhibitor of estimated protein. The AutoDock 4.0 program is used for molecular docking simulations. Anthrarufin, its monoanion and dianion can be considered as a potential HIV-1 RT inhibitors because they have similar inhibitory potency to other ligands under consideration, according to the results of the free energy of binding (∆Gbind) and inhibition constant (Ki) values.
Kinetics of the substitution reactions between monofunctional Au(III) complexes, Au(dien)Cl
2+
, Au(bpma)Cl
2+
and Au(terpy)Cl
2+
(dien = 3-azapentane-1,5-diamine, bpma = di-(2-picolyl) amine, terpy ...= 2,2′;6′,2″-terpyridine), and biologically relevant sulphur ligands, namely glutathione (GSH),
l
-methionine (
l
-Met) and
l
-cysteine (
l
-Cys), were studied in 0.1 M HCl (pH = 1.0). The reactions were followed under
pseudo
-first-order conditions as a function of ligand concentration and temperature using stopped-flow spectrophotometry. The Au(terpy)Cl
2+
complex proved to be more reactive than the Au(bpma)Cl
2+
and Au(dien)Cl
2+
complexes. The reactivities of the nucleophiles follow the same order for all three complexes, viz.
l
-Met > GSH >
l
-Cys. Values of the activation parameters of the reactions support an associative substitution mechanism. In order to confirm that these monofunctional Au(III) complexes undergo a single substitution process in strongly acidic medium, the reaction between Au(terpy)Cl
2+
and
l
-Met was studied by HPLC. At pH = 1.0, only one reaction product was detected.
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