ABSTRACT
Ovarian cancer has the worst case-to-fatality ratio of all gynecologic malignancies. The main reasons for the high mortality rate are relapse and the development of chemoresistance. In this paper, the cytotoxic activity of two new multiaction platinum(IV) derivatives of cisplatin and oxaliplatin in a panel of ovarian cancer cells is reported. Cis,cis,trans-[Pt(NH3)2Cl2(IPA)(DCA)] (1) and trans-[Pt(DACH)(OX)(IPA)(DCA)] (2) (IPA = indole-3-propionic acid, DCA = dichloroacetate, DACH = 1R,2R-1,2-diaminocyclohexane, OX = oxalate) were synthesized and characterized by elemental analysis, ESI-MS, FT-IR, and 1H, 13C, and195Pt NMR spectroscopy. The biological activity was evaluated in A2780, PEA1, PEA2, SKOV3, SW626, and OVCAR3 cells. Both complexes are potent cytotoxins. Remarkably, complex 2 is 14 times more active in OVCAR3 cells than cisplatin and is able to overcome cisplatin resistance in PEA2 and A2780cis cells, which are models of post-treatment patient-developed and laboratory-induced resistance. This complex also shows activity in 3D cancer models of the A2780 cells. Mechanistic studies revealed that the complexes induce apoptosis via DNA damage and ROS generation.
Subject(s)
Antineoplastic Agents , Apoptosis , Drug Screening Assays, Antitumor , Ovarian Neoplasms , Humans , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Female , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Apoptosis/drug effects , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Organoplatinum Compounds/pharmacology , Organoplatinum Compounds/chemistry , Organoplatinum Compounds/chemical synthesis , Reactive Oxygen Species/metabolism , Molecular Structure , Cell Proliferation/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Cisplatin/pharmacology , Structure-Activity Relationship , Dose-Response Relationship, DrugABSTRACT
The shelf life of horticultural commodities depends on pre- and postharvest factors, such as soil fertilization and postharvest handling. The current study aimed to evaluate fresh-cut celery's postharvest quality as affected by the rate and type (organic and chemical) of nitrogen (N) fertilizer and postharvest treatments. Celery ('Tall Utah') crop was grown in a field in Karaj, Iran. The experimental design was a randomized complete block with three replications and seven preharvest (fertilizer), and five postharvest treatments. Organic fertilizers were vermicompost (VER) and bio-organic fertilizer [farmyard and livestock manure plus Trichoderma harzianum (COM)]. Chemical fertilizers were urea (46% N) at high rate [322 kg·ha1 N (UREA_HIGH)], optimal rate [196 kg·ha-1 N (UREA_OPT)], and low rate [138 kg·ha-1 N (UREA_LOW)]; ammonium nitrate [35% N (AN)] at 196 kg·ha-1 N; and treatment without fertilization was used as a control. Postharvest treatments included plastic packaging (PP), hydrocooling (HC), blanching (B), and edible coating of psyllium seed mucilage (EC). After postharvest treatments, celery petioles were stored (0-2°C, 85%-90% RH) for 4 weeks and evaluated weekly for quality attributes. Organic fertilizers and UREA_LOW were the most effective treatments in reducing the changes in color, weight loss, titratable acidity (TA), pH, and total soluble solids (TSS) of fresh-cut celery. Organic fertilizers enhanced the vitamin C content, total phenols, and antioxidant activity in celeries. As postharvest treatments, hydrocooling, plastic packaging, and blanching maintained chroma and hue values. Blanching had the greatest effect on the L* value. Hydrocooling increased celery's TA, TSS, and vitamin C content and reduced weight loss and pH during storage. Thus, celery quality was improved when grown under low or adequate N fertilization. Hydrocooling was an effective postharvest treatment for preserving fresh-cut celery quality during storage.
ABSTRACT
Considering the importance of spice plants and their shelf life, as affected by various factors, the current study considered Summer savory plants (Satureja hortensis cv. Saturn) for evaluation under the application of different concentrations of ammonium sulfate (0, 40, 60, 80, and 100 kg/ha) as primary treatments. Based on the plant response, the control group and 100 kg/ha ammonium sulfate were selected as suitable treatments for storage experiments (i.e., storage at ambient, refrigerator, and freezer temperatures for 8 months). Based on the results, the highest percentage and yield of S. hortensis essential oil and biomass occurred in response to 100 kg ammonium sulfate, whereas the lowest amounts were observed in the control group (i.e., in the absence of ammonium sulfate). During the storage period, the essential oil content decreased, but the carvacrol content of the essential oil increased. During the different durations and conditions of storage, the stability of secondary metabolites varied. Essential oil, rosmarinic acid, and carvacrol contents maintained greater stability in plants treated with ammonium sulfate (100 kg/ha), compared with the control group during the storage period. It can be concluded that the preharvest application of ammonium sulfate on S. hortensis improved plant growth and quality indices at preharvest time, while also maintaining the stability of its active ingredients at the postharvest stage and storage time. It also led results to recommend storing Summer savory in the freezer to better preserve its secondary metabolites.
ABSTRACT
A series of gold(I) complexes with the general formula [Au(L2)(L')] (L2=4-phenyl-N-(prop-2-yn-1-yl)quinazoline-2-carboxamide, L'=PPh3 (triphenylphosphine), 1; TPA (1,3,5-triaza-7-phosphaadamantane), 2, and Me2-imy (1,3-dimethylimidazol-2-ylidene), 3) were synthesized and fully characterized by spectroscopic methods. The alkynyl ligand L2 belongs to the quinazoline carboxamide class of ligands that are known to bind to the translocator protein (TSPO) at the outer mitochondrial membrane. 1 and 2 exert cytotoxic effects in bladder cancer cells with IC50 values in the low micromolar range. Further mechanistic analysis indicated that the two complexes both act by inducing reactive oxygen species and caspase-mediated apoptosis. The complexes inhibit thioredoxin reductase, an established target of anticancer gold(I) complexes. Docking studies confirmed that after ligand exchange the free ligand L2 can interact with the TSPO binding site.
ABSTRACT
The effects of mycorrhization (inoculation and non-inoculation) on growth and quality of two ecotypes (Baft and Ramjerd) of Glycyrrhiza glabra L. under heavy metals stress (0, 300 Pb + 20 Cd (H1) and 600 Pb + 40 Cd (H2) (mg kg-1) was investigated. Higher concentration of heavy metals decreased shoot dry weight in Baft (7.05%) and Ramjerd (43.34%) than control. Root dry weight increased in mycorrhizal Baft (28.23%) and Ramjerd (31.84%) ecotypes under H2 than non-mycorrhizal plants. In mycorrhizal plants, root colonization percentage decreased 37.07% in H2 than control. Increasing heavy metals concentration led to increase of total antioxidant activity and total phenol content. Mycorrhizal Ramjerd showed the lowest shoot Pb concentration in both heavy metals concentrations and the highest root Pb concentration (107.25% higher than non-mycoorhizal one) in H2. For both ecotypes, the lowest shoot Cd concentration observed in mycorrhizal plants under H1 and mycorrhizal plants had more root Cd concentration (33.83 mg kg-1 dry matter) than non-mycorrhizal ones. In both concentrations of heavy metals, the lowest Pb (0.026) and Cd (0.153) translocation factor (TF) observed in mycorrhizal plants. Based on the results, licorice with TF< 1 is not a hyperaccumulator plant but stabilizes Cd and Pb in root. Novelty statement: Licorice is a well-known medicinal plant that its root and rhizome contains diverse applications in pharmaceutical and food industries. The main source of licorice supply is through harvesting from natural habitats of Iran (one of the first exporters of licorice in the world), which during the last years have been exposed to heavy metals contamination. Therefore, the growth response of the plant in polluted habitats and most importantly, the concentration of heavy metals especially in belowground parts of the plant need more consideration. Hence, this research was carried out with an objective to investigate growth and yield potential response of two ecotypes of licorice to mycorhization under heavy metal stress (Cd and Pb) and the mechanism of heavy metal management in above and belowground parts of licorice in order to achieve its potential for further sustainable phytoremediation programs and most importantly considering the heavy metal accumulation in rhizomes and roots in accordance with world standards for medicinal and edible consumption.
Subject(s)
Glycyrrhiza , Metals, Heavy , Soil Pollutants , Biodegradation, Environmental , Cadmium , Iran , Lead , Metals, Heavy/analysis , Plant Roots/chemistry , Soil Pollutants/analysisABSTRACT
Two ferrocenyl derivatives, Fc-CA and Fc-FA, were synthesized by a condensation reaction between the amino ferrocene and hydroxycinnamic acids, that is, caffeic acid (CA) and ferulic acid (FA). The structures and purity of all compounds were characterized by 1H- and 13C NMR spectroscopies, Mass spectrometry (MS), and elemental analysis. The antioxidant properties of Fc-CA and Fc-FA and of its ligand were studied for free radical scavenging activity toward DPPHâ¢, superoxide anion (O2â¢-), NOâ¢, and ABTSâ¢+ by UV-vis and electron spin resonance spectroscopies. The cytotoxicity of Fc-CA and Fc-FA against MCF-7 and MDA-MB-231 breast cancer cells and MRC-5 human lung fibroblasts cell was higher than that of cisplatin. The geometry and electronic structures of all compounds were then simulated using density functional theory at M05-2X/6-311+G(d,p) level of theory. Thermodynamics of the free radical quenching reactions by common mechanisms reveal the higher antioxidant properties of the Fc-CA and Fc-FA in comparison to their ligands. An in-depth study of the free radical scavenging activity against HOO⢠and HO⢠radicals was performed for two of the most favorable and competitive mechanisms, the hydrogen transfer (either hydrogen atom transfer or proton-coupled electron transfer mechanisms) and the radical adduct formation. The in silico studies indicated that ferrocenyl derivatives exhibited prominent binding affinity to protein models in comparison to CA and FA. Their dock scores were notable at ligand binding sites of ERα, Erß, and JAK2 proteins. Dock pose analysis also shed light into the possible mechanism of action for the studied compounds.
Subject(s)
Antioxidants , Models, Theoretical , Antioxidants/pharmacology , Free Radical Scavengers , Free Radicals , Humans , Metallocenes , ThermodynamicsABSTRACT
BACKGROUND: Although very few studies have investigated the association of narcissistic symptoms and aggressive driving, very little is known about association of narcissism and serious traffic outcomes such as crash and serious violation of traffic laws. The aim of this study was to determine whether there is an association between the narcissistic symptoms of professional bus drivers and high risk driving records or crash. METHODS: A total of 200 outer-city bus drivers were enrolled in 2018 from Tehran origin of trips. The narcissistic symptoms of drivers were assessed using the Narcissistic Personality Inventory-16 (NPI-16). The traffic police databases were searched for records of crashes or recorded negative traffic scores during a 3-year period prior to time of interviews. Data were analyzed using Stata 14 statistical software package. RESULTS: Mean age of the participants was 44.4 years with a standard deviation of 9.3 years. Fourteen drivers (7%) had a crash history over the past three years. Mean normalized narcissism score was 22.3 among those without a crash history over the past three years versus 18.8 among those with a crash history without statistical significance. Forty-four drivers (22%) had a negative traffic scoring record due to high risk traffic violations registered in police database over the past three years. Mean normalized narcissism score was 22 among those without negative score record over the past three years versus 22.3 among those with a negative score history. However, the difference was not found to be statistically significant. CONCLUSIONS: The findings of present study does not support an association between crash risk or being a recorded high risk driver and narcissism levels. However, considering the complex risk profile of road traffic crashes, much larger studies are needed to rule it out.
ABSTRACT
The design, synthesis, characterization, and biological activity of a series of platinum(IV) prodrugs containing the axial ligand 3-(4-phenylquinazoline-2-carboxamido)propanoate (L3) are reported. L3 is a derivative of the quinazolinecarboxamide class of ligands that binds to the translocator protein (TSPO) at the outer mitochondrial membrane. The cytotoxicities of cis,cis,trans-[Pt(NH3)2Cl2(L3)(OH)] (C-Pt1), cis,cis,trans-[Pt(NH3)2Cl2(L3)(BZ)] (C-Pt2), trans-[Pt(DACH)(OX)(L3)(OH)] (C-Pt3), and trans-[Pt(DACH)(OX)(L3)(BZ)] (C-Pt4) (DACH: R,R-diaminocyclohexane, BZ: benzoate, OX: oxalate) in MCF-7 breast cancer and noncancerous MCF-10A epithelial cells were assessed and compared with those of cisplatin, oxaliplatin, and the free ligand L3. Moreover, the cellular uptake, ROS generation, DNA damage, and the effect on the mitochondrial function, mitochondrial membrane potential, and morphology were investigated. Molecular interactions of L3 in the TSPO binding site were studied using molecular docking. The results showed that complex C-Pt1 is the most effective Pt(IV) complex and exerts a multimodal mechanism involving DNA damage, potent ROS production, loss of the mitochondrial membrane potential, and mitochondrial damage.
Subject(s)
Antineoplastic Agents/pharmacology , Mitochondria/drug effects , Organoplatinum Compounds/pharmacology , Prodrugs/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Cisplatin/pharmacology , DNA Damage/drug effects , Epithelial Cells/drug effects , Humans , Ligands , MCF-7 Cells , Mitochondrial Membranes/drug effects , Oxaliplatin/pharmacology , Reactive Oxygen Species/metabolismABSTRACT
A new cyclometalated Au(III) complex highlighting a naphthoquinone-C^N scaffold with formula (NQ-N^C)AuIII(SAd)Cl, 1, in which NQ-N^C: 2-(5-amino-benzo[h]quinolone)-3-(3-methyl-2-butenyl)-1,4-naphthoquinone, HSAd: 1-adamantanethiol, was synthesized and characterized. The interaction of complex 1 with cysteine (CysH) was experimentally and theoretically studied. Complex 1 was more active against MCF-7 and A549 cancer cell lines and less active in a healthy cell (non-tumorigenic cells, MRC-5) than cisplatin. The DNA binding and inhibition of thioredoxin reductase of complex 1 were studied and compared with the molecular docking results. The generation of reactive oxygen species (ROS) and apoptosis of this new complex were also investigated.
Subject(s)
Antineoplastic Agents/pharmacology , Cytotoxins/pharmacology , Enzyme Inhibitors/pharmacology , Organogold Compounds/pharmacology , Thioredoxin-Disulfide Reductase/antagonists & inhibitors , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Cytotoxins/chemical synthesis , Cytotoxins/chemistry , Density Functional Theory , Drug Screening Assays, Antitumor , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Humans , Molecular Structure , Organogold Compounds/chemical synthesis , Organogold Compounds/chemistry , Thioredoxin-Disulfide Reductase/metabolismABSTRACT
A novel cyclometalated gold(iii) complex supported by chlorambucil coupled with phenylpyridine (CHL-N^C) and a hybrid of vitamin B1 with dithiocarbamate (B1-DTC) with the formula [(CHL-N^C)AuIII(B1-DTC)](Cl2), 1, was synthesized and fully characterized using different techniques, including multinuclear NMR, mass spectrometry, and elemental analysis. This complex is water-soluble and stable in a biological environment. This new complex offers a new scaffold to explore the biological properties of gold(iii) complexes as an anticancer drug. The antiproliferative activities of complex 1 and free ligands against breast and colon cancer cells showed auspicious results with IC50 values in the micromolar range for complex 1 and more active than cisplatin and free ligands with selectivity over non-tumorigenic cells human lung fibroblasts, MRC-5. The DNA binding and inhibition of thioredoxin reductase of complex 1 were studied and compared with molecular docking results. Moreover, the Au cellular uptake and apoptosis of this new complex were investigated.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis , Chlorambucil/pharmacology , Coordination Complexes/pharmacology , Gold/chemistry , Neoplasms/drug therapy , Thiamine/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents, Alkylating/chemistry , Antineoplastic Agents, Alkylating/pharmacology , Chlorambucil/chemistry , Cisplatin/pharmacology , Coordination Complexes/chemistry , Drug Screening Assays, Antitumor , HCT116 Cells , Humans , Ligands , MCF-7 Cells , Molecular Docking Simulation , Molecular Structure , Neoplasms/pathology , Thiamine/chemistry , Vitamin B Complex/chemistry , Vitamin B Complex/pharmacologyABSTRACT
A new oxidovanadium(IV) complex VO(L)(Jug) (HL = 5-methoxy-1,3-bis (1-methyl-1H-benzo[d]imidazol-2-yl)benzene, Jug = juglone) was synthesized and characterized. Interactions of the V(IV) complex with calf thymus DNA (CT DNA) and human serum albumin were studied using different techniques such as UV-vis and fluorescence emission spectroscopy. The experimental results were confirmed by the molecular docking study. The oxidovanadium(IV) complex can efficiently cleave pUC19 DNA in the presence of Hydrogen peroxide. Also, the in vitro cytotoxicity properties of the oxidovanadium(IV) complex was evaluated against MCF-7, HPG-2 and HT-29 cancer cell lines and HEK293 non-malignant fibroblasts were evaluated and compared with free ligands, VOSO4 and cisplatin as reference drugs.Communicated by Ramaswamy H. Sarma.
Subject(s)
DNA/chemistry , Naphthoquinones/chemistry , Naphthoquinones/pharmacology , Serum Albumin, Human/chemistry , Vanadium/chemistry , Vanadium/pharmacology , Binding Sites , Cell Death/drug effects , Cell Line, Tumor , DNA Cleavage/drug effects , Humans , Molecular Conformation , Molecular Docking Simulation , Protein Binding , Spectrometry, FluorescenceABSTRACT
Here we report the design and synthesis of a chlorambucil-alkynyl (CHL-CCH) ligand, mononuclear gold(i) complex K[(CHL-CC)AuCl], 1, and heteronuclear complex (CHL-CC)Au(µ2-η2-CS3)Ti(η5-Cp)2, 2 for renal cancer. Complex 2 is significantly more cytotoxic than complex 1 and cisplatin against renal cancer cells with a high selectivity index value. The mechanism of action of these complexes against renal cancer cells was studied in detail by experimental and computational methods.
Subject(s)
Antineoplastic Agents/pharmacology , Chlorambucil/analogs & derivatives , Chlorambucil/pharmacology , Coordination Complexes/pharmacology , Enzyme Inhibitors/pharmacology , Thioredoxin-Disulfide Reductase/antagonists & inhibitors , Antineoplastic Agents/chemical synthesis , Apoptosis/drug effects , Cell Line, Tumor , Chlorambucil/chemical synthesis , Coordination Complexes/chemical synthesis , Density Functional Theory , Drug Design , Enzyme Inhibitors/chemical synthesis , Gold/chemistry , Humans , Kidney Neoplasms/drug therapy , Models, Chemical , Molecular Docking Simulation , Titanium/chemistryABSTRACT
A Cu(II) complex, that is, [Cu(CNC-B3)(IM-B7)](PF6)2, 1, containing CNC-B3 (L2) = CNC-pincer-vitamin B3 and IM-B7 (L3) = 1H-imidazole-1-methanamine-vitamin B7 conjugates, was developed as a potential chemotherapeutic agent for breast cancer cell lines. The Cu(II) complex brings about a remarkable in vitro cytotoxicity in comparison with cisplatin and tamoxifen against MDA-MB-231 and MCF-7 cancer cell lines. Interestingly, the Cu(II) complex was considerably less toxic to MRC-5 normal cells. The DNA/human serum albumin-binding capacity of the Cu(II) complex was confirmed by spectrometric methods and the molecular docking and ONIOM studies. The mechanistic pathway of DNA cleavage was studied by reactive oxygen species (ROS)-inhibiting agents. Furthermore, the Cu(II) complex affected the increasing level of the reactive oxygen species (ROS) and the decreasing level of glutathione in MCF-7 cells. The new complex induced major levels of MCF-7 cancer cell death by apoptosis.
Subject(s)
Antineoplastic Agents/therapeutic use , Biotin/chemistry , Breast Neoplasms/drug therapy , Copper/chemistry , Niacin/chemistry , Organometallic Compounds/therapeutic use , Antineoplastic Agents/metabolism , Apoptosis/drug effects , DNA/metabolism , DNA Cleavage/drug effects , Drug Stability , Female , Glutathione/metabolism , Humans , Inhibitory Concentration 50 , MCF-7 Cells , Molecular Docking Simulation , Organometallic Compounds/metabolism , Protein Binding , Reactive Oxygen Species/metabolism , Serum Albumin, Human/metabolismABSTRACT
The new heteronuclear molybdocene-gold complex 1, [(η5-Cp)2MoII[(µ2-η2-dtc)2Nap]AuIII(LC)](PF6), (η5-Cp: η5-cyclopentadienyl, (dtc)2Nap: 2,7-bis(dithiocarbamate)naphthalene, LC: lidocaine) was synthesized and evaluated for biological activity. With the aim of assessing the possible DNA-binding mode, the interaction of the complex 1 with calf thymus DNA (CT DNA) was investigated by UV spectroscopy, emission titration, and viscosity measurement. Also, the binding of the complex to human serum albumin (HSA) was considered by UV-Vis and fluorescence emission spectroscopy. Moreover, molecular docking was used for modeling of the binding of the complex to DNA and HSA. These experimental results were confirmed by the results of molecular docking concerning the lowest binding energy. The cytotoxicity of the heterometallic complex 1 has been evaluated against a panel of several cancer cell lines with low micromolar IC50 (72 h) values, according to its cellular uptake and also versus HEK293 nonmalignant fibroblasts. Moreover, the complex 1 showed the induction of apoptotic process. Communicated by Ramaswamy H. Sarma.
Subject(s)
Antineoplastic Agents/pharmacology , DNA/metabolism , Gold/chemistry , Lidocaine/chemistry , Neoplasms/pathology , Organometallic Compounds/chemistry , Serum Albumin, Human/metabolism , Antineoplastic Agents/chemistry , Binding Sites , Cell Proliferation , DNA/chemistry , HEK293 Cells , Humans , Molecular Structure , Neoplasms/drug therapy , Nucleic Acid Conformation , Protein Binding , Protein Conformation , Serum Albumin, Human/chemistry , Tumor Cells, CulturedABSTRACT
The new cyclometalated ruthenium(ii) complex, [Ru(CCC-Nap)(Ibu)(PTA)] was designed and synthesized using ibuprofen (Ibu), 1,3,5-triaza-7-phosphaadamantane (PTA) and CCC-pincer containing naproxen moiety (CCC-Nap) as ligands. The compounds were fully characterized by elemental analysis, FT-IR, multinuclear (1H, 13C, and 31P) NMR spectroscopy, and electrospray ionization mass spectrometry. The cytotoxicity of the newly synthesized Ru(ii) complex was found to be low, and the complex was about twice as active as cisplatin with IC50 values in the range of 0.9-1.32 µM for both MCF-7 and MDA-MB-231 cell lines. Cyclooxygenase (COX) inhibition studies revealed that the Ru(ii) complex displayed strong interactions with COX-2, about 16 and 5 times more than free Ibu and CCC-Nap ligands, respectively. The Ru(ii) complex improved the production of reactive oxygen species (ROS) by 10.7 fold compared to the control (H2O2 as a positive control) in MCF-7 cells. Quantum chemical calculations gave more insights into the geometry and electronic properties of the novel Ru(ii) complex, while molecular docking provided theoretical information on the interactions of Ru(ii) complex with human cyclooxygenase-2 (COX-2) and the results were compared with those of the interactions of the free ligands with COX-2.
Subject(s)
Antineoplastic Agents/chemical synthesis , Coordination Complexes/chemical synthesis , Cyclooxygenase Inhibitors/chemical synthesis , Ruthenium/chemistry , Adamantane/analogs & derivatives , Adamantane/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Cyclooxygenase Inhibitors/chemistry , Cyclooxygenase Inhibitors/pharmacology , Drug Stability , HEK293 Cells , Humans , Ibuprofen/chemistry , Ligands , MCF-7 Cells , Molecular Docking Simulation , Molecular Structure , Naproxen/chemistry , Organophosphorus Compounds/chemistry , Reactive Oxygen Species/metabolismABSTRACT
A new copper(ii) complex, [Cu(LC)(Ibu-phen)(H2O)2](ClO4)2 (LC: lidocaine, Ibu-phen: ibuprofen amide-phenanthroline), was synthesized and characterized. The antioxidant activities of the free ligands and the copper(ii) complex were evaluated by in vitro experiments and theoretical calculations using density functional theory (DFT). Structures of the ligand Ibu-phen and the complex were identified by 1H and 13C NMR, FT-IR spectroscopies, mass spectrometry, thermogravimetric analysis and elemental analysis. The antioxidant potentials of LC and Ibu-phen ligands as well as copper(ii) complex were also evaluated by DPPHË, ABTSË+, HOË essays and EPR spectroscopy. The experimental results show that the radical scavenging activity (RSA) at various concentrations is decreased in the following order: copper(ii) complex > ascorbic acid > LC > Ibu-phen. Structural and electronic properties of the studied compounds were also analyzed by DFT approach at the M05-2X/6-311++g(2df,2p)//M05-2X/LanL2DZ level of theory. ESP maps and NPA charge distributions show that the highly negative charge regions found on the N and O heteroatoms make these sites more favorable to bind with the central copper ion. Frontier orbital distributions of copper(ii) complex indicate that HOMOs are mainly localized at Ibu-phen, while its LUMOs are distributed at LC. Based on natural bond orbitals (NBO) analyses, Cu(ii) ion plays as electron acceptor in binding with the two ligands and two water molecules. Thermochemical properties including bond dissociation enthalpy (BDE), ionization energy (IE), electron affinity (EA), proton affinity (PA) characterizing three common antioxidant mechanisms i.e. hydrogen transfer (HT), single electron transfer (SET) and proton loss (PL) were finally calculated in the gas phase and water solvent for two ligands and the copper(ii) complex at the same level of theory. As a result, the higher EA and lower BDE and PA values obtained for copper(ii) complex show that the complex shows higher antioxidant potential than the free ligands.
ABSTRACT
An Ir(iii) complex was synthesized using mixed ligands of biological importance, namely ibuprofen, flavonol and 2-phenylpyridine. The compound was characterized by 1H-NMR, 13C-NMR and TOF-MS spectroscopies and elemental analysis. Structures of the complex and its ligands were also calculated by density functional theory using B3LYP/Lanl2dz//6-31G(d) level of theory. Analyses of electrostatic potential, natural population, and frontier orbitals of the molecules as well as the calculation of intrinsic thermochemical properties such as bond dissociation enthalpy, ionization potential, electron affinity and proton affinity in the gas phase and in solvents (water and pentylethanoate) give the first indication that the complex is a potential antioxidant. The latter even shows better antioxidant capacity than the parent ligands. The antioxidant properties of the complex and its ligands were experimentally evaluated by studying the free radical scavenging activity towards HOË, NOË, DPPHË and ABTSË+ radicals. Further computational work on the antioxidant processes such as the single electron transfer, the proton loss, the formal hydrogen transfer (FHT) and the radical adduct formation reactions was conducted. Results show that the FHT reaction is the mechanism responsible for the radical scavenging activity of the complex towards HOË, HOOË, NOË and DPPHË radicals while ABTSË+ seems to be scavenged by an electron-donating mechanism. The FHT was further determined as a hydrogen-atom transfer but not a proton-couple electron transfer mechanism.
ABSTRACT
A new cyclometallated platinum(ii) complex with 1-adamantanemethylcyanamide (1-ADpcydH) and 2-[amino(2-phenylpyridine)]-1,4-naphthoquinone (1,4-NQ) ligands with the formula cis-Pt(1,4-NQ)(1-ADpcyd)(H2O) was synthesized and fully characterized. Cellular uptake, DNA platination, and cytotoxicity against human MCF-7 breast, HepG-2 liver hepatocellular carcinoma, and HT-29 colon cancer cell lines were evaluated. The interaction of guanine (G) with cis-Pt(1,4-NQ)(1-ADpcyd)(H2O) was studied by 195Pt NMR and mass spectroscopy. Furthermore, DFT calculations were performed on the complexes cis-Pt(1,4-NQ)(1-ADpcyd)(H2O) 1 and cis-Pt(1,4-NQ)(1-ADpcyd)(G) 2 using the BP86-D and B3LYP functionals, in order to gain deeper insights into the molecular and electronic structures. Decomposition energy analysis gave a clear understanding of the bonding within both complexes, showing that the interactions were governed by two-third ionic and one-third covalent characters, which were stronger between the guanine and the Pt(ii) center than those between water and the Pt(ii).
ABSTRACT
New multinuclear gold(iii), palladium(ii) pincer complexes containing bis(diphenylphosphino) ferrocene/non-ferrocene ligands of formula [(L)Au(µ2-η2-CS3)Pd(dppf)](PF6)2, 1, and [(L)Au(µ2-η2-CS3)Pd(dppe)](PF6)2, 2 (HL = 5-methoxy-1,3-bis (1-methyl-1H-benzo[d]imidazol-2-yl)benzene, dppf = 1,1'-bis(diphenylphosphino)ferrocene, and dppe = bis(diphenylphosphino)ethane) have been synthesized and fully characterized. Both complexes are more cytotoxic to a number of human cancer cell lines than cisplatin. Moreover, complex 1 is more active than auranofin as the reference gold compound against a panel of several human tumor cell lines. Chemosensitivity tests completed on cisplatin sensitive and resistant cell lines have confirmed that both complexes were able to overcome cisplatin resistance. The complexes successfully inhibited the enzymes thioredoxin reductase (TrxR) and glutathione reductase (GR). The cellular uptake of both gold and palladium of the complexes was studied, which indicated a high biological stability of the complexes. The complexes 1 and 2 increase the production of ROS in HCT-15 cells. In addition, these complexes induce major levels of cancer cell death by apoptosis.
ABSTRACT
The successful design, synthesis, characterization, photophysical properties and anticancer mechanistic studies of a series of half-sandwich cyclopentadienyl iridium(iii) complexes of the type [Cp*IrIII(LC)(L1)](PF6), 1, and [Cp*IrIII(LC)(L2)](PF6), 2, in which Cp* = pentamethylcyclopentadienyl, L1 = 4-(pyren-10-yl)ethynyl-phenylcyanamide, L2 = 4'-(pyren-10-yl)ethynyl-4-cyanamidobiphenyl, and LC = lidocaine, are reported for their application as photodynamic therapy (PDT) agents. The DNA binding, DNA photocleavage, cellular uptake, and apoptosis of the complexes have also been studied.