Non-steroidal Anti-inflammatory Drugs Naproxen Research Articles

Functional food property of honey locust (Gleditsia triacanthos) flowers

The use of honey locust in food prompted us to study its flowers for functional food constituents. Bioassay-guided purification of hexane, ethyl acetate and methanolic extracts of its flowers afforded three new betulinic acid esters (1–3), one new linalool carboxylic acid ester (4), known terpenoids (5–7) and known polyphenols (8–11), as elucidated by spectroscopic methods. The extracts and terpenoids 1–7 were tested for antiinflammatory and antioxidant activities against cyclooxygenase enzymes (COX-1 and -2) and lipid peroxidation (LPO), respectively. Compounds 1–7 at 25 µg/mL showed antiinflammatory activity as indicated by COX-1 and -2 enzymes inhibition at a range of 40–50% and 33–37%, respectively. The antiinflammatory activity of extracts at 100 and compounds at 25 µg/mL was superior to aspirin and comparable to other over the counter non-steroidal antiinflammatory drugs (NSAIDs) naproxen and ibuprofen. Compounds 1–7 did not show LPO activity.

Nonsteroidal anti-inflammatory drugs in-vitro and in-vivo treatment and Multidrug Resistance Protein 4 expression in human platelets

Platelet Multidrug Resistance Protein 4 (MRP4)-overexpression has a role in reducing aspirin action in patients after by-pass surgery. Aspirin induces platelet MRP4 over-expression, through megakaryocytes genomic modulation.Aim of our work was to verify whether other non-steroidal antiinflammatory drugs (NSAIDs) enhance platelet MRP4 expression and evaluate platelet function in patients who overexpressed MRP4.We evaluated MRP4-mRNA in a human megakacaryoblastic cell line (DAMI), treated with both COX-2 inhibitor (celecoxib) and traditional NSAIDs (diclofenac and naproxen). Osteoarthritis patients, who reported to take NSAIDs twice a week for at least four continuous weeks and a control population, who didn't take any drugs during the previous month, were enrolled. We evaluated platelet MRP4 amount, by both mRNA levels and protein expression (Western-Blot) and ADP induced platelet aggregation.DAMI cells treated with celecoxib, diclofenac, and naproxen showed a significant increase in MRP4-mRNA expression compared to the mock culture.Osteoarthritis patient platelets presented a higher expression of MRP4 (both at mRNA and protein levels) and an increase in ADP-induced platelet aggregation compared to the control population.NSAID treatment induced platelet MRP4 overexpression. Osteoarthritis patients, who overexpress MRP4, showed platelet hyper-reactivity.These evidences could explain in part the increased cardiovascular risk present during NSAID treatment.

Effects of mono and dinuclear copper(II) complexes derived from non-steroidal anti-inflammatory drug naproxen on human serum paraoxanase1 (PON1) activity

The inhibition of human paraoxonase 1 (PON1, EC 3.1.8.1) enzyme, with two Cu(II) complexes derived from naproxen was investigated by using the paraoxonase activity method with diethyl 4-nitrophenyl phosphate as substrate. The complexes [Cu 2 (µ-nap) 4 (3-pic) 2 ] (1) and [Cu(nap) 2 (H 2 O)(4-pic) 2 ] (2) decreased the in vitro PON1 activity with different inhibition mechanisms. The inhibition mechanism of complex 1 was uncompetitive whereas complex 2 was noncompetitive inhibitors. In this study, complexes mentioned above showed effective inhibitory activity on PON1. IC 50 values for [Cu 2 (µ-nap) 4 (3-pic) 2 ] (1) and [Cu(nap) 2 (H 2 O)(4-pic) 2 ] (2) were of 0.109 mM and 0.103 mM for PON1, respectively. K i values for complex 1 and complex 2 were of 0.116 mM and 0.121 mM for PON1, respectively.

Deciphering the pathogenesis of NSAID enteropathy using proton pump inhibitors and a hydrogen sulfide-releasing NSAID.

The small intestine is a significant site of ulceration and bleeding induced by nonsteroidal anti-inflammatory drugs (NSAIDs). The pathogenesis is poorly understood. The present study explored the roles of bile, bacteria, and enterohepatic circulation to NSAID enteropathy, using both a conventional NSAID (naproxen) and a gastrointestinal-safe naproxen derivative (ATB-346), as well as proton pump inhibitors (PPIs). Rats were treated orally with naproxen or equimolar doses of ATB-346 over a 5-day period, with or without PPI administration, and intestinal damage was quantified. The cytotoxicity of bile from the rats was evaluated in vitro. Biliary excretion of naproxen and ATB-346 was determined. The impact of the NSAIDs and of PPIs on the composition of the intestinal microbiota was examined by deep sequencing of 16s rRNA. Naproxen caused significant intestinal damage and inflammation, whereas ATB-346 did not. Naproxen, but not ATB-346, dose dependently increased the cytotoxicity of bile, and it was further increased by PPI coadministration. Whereas biliary excretion of naproxen was significant in naproxen-treated rats, it was greatly reduced in rats treated with ATB-346. The enteric microbiota of naproxen-treated rats was distinct from that in vehicle- or ATB-346-treated rats, and PPI administration caused significant intestinal dysbiosis. The increase in cytotoxicity of bile induced by naproxen and PPIs may contribute significantly to intestinal ulceration and bleeding. Some of these effects may occur secondary to significant changes in the jejunal microbiota induced by both naproxen and PPIs.

Naproxen-Enriched Artificial Sediment Induces Oxidative Stress and Genotoxicity in Hyalella azteca

The nonsteroidal anti-inflammatory naproxen sodium is among the most commonly used pharmaceuticals in Mexico. Nevertheless, there is no adequate regulation to control its sale, use, and disposal. This agent can enter water bodies by diverse pathways, attaining significant concentrations, especially in sediments since they are the final reservoir of many organic contaminants, and may induce damage on hydrobionts. Naproxen sodium is water-soluble, shows stability in aquatic ecosystems, and can form reactive products when oxidized. The aim of this study was to evaluate the oxidative stress and consequent damage to genetic material induced by naproxen sodium in sediments on Hyalella azteca. After 48 h of exposure to artificial sediments enriched with 76.6 and 339.2 mg kg−1 (equivalent to 1/10 of the LC50 and the NOAEL obtained in an earlier 48-h acute toxicity assay), the following biomarkers were evaluated: lipid peroxidation level, protein carbonyl content, activity of the antioxidant enzymes, and DNA damage. Results show that naproxen sodium induces oxidative stress (increased lipid and protein oxidation, as well as superoxide dismutase and catalase activity and decrease of glutathione peroxidase activity) and genotoxicity (increased oxidative damage of DNA) at sublethal concentrations on H. azteca, being the damage, concentration dependent.

Inhibitory Effect of Meclofenamate Sodium on Proteasome Activity in the Cardiac Cells and Reversal of its Effect by Antioxidants

Objective: Prolonged use of nonsteroidal anti-inflammatory drugs (NSAIDs) is reported to increase the occurrences of cardiovascular diseases (CVD). Significant proteasome inhibition is also associated with increased incidences of CVD. Hence, the effect of the NSAIDs meclofenamate sodium (MS) and naproxen sodium (NAP) on the proteasome system was investigated in H9c2 rat cardiac cells. Methods: 26S proteasome activity assays, cell viability assays, reactive oxygen species (ROS) assays, and MV151 fluorescent labelling of proteasome active sites were utilized. Results: Decreased 26S β5 chymotrypsin-like proteasome activity (30%) and β1 caspase-like activity (20%) was seen in H9c2 cells treated with 100µM MS for 24h compared to the cells treated with 500 µM NAP or vehicle. Rat heart lysates showed significant decreases in β5 activity in the presence of 50-500 µM MS. Purified proteasomes also showed decreased β5 activity in the presence of 100 µM MS. MV-151 labeling showed that this decrease in activity was not due to direct interaction between MS and the proteasome active sites. Both NSAIDs caused increased ROS levels in H9c2 cells but the rate of ROS formation was significantly higher in cells treated with 100 µM MS than 500 µM NAP after 2hrs. MS (100 µM) but not NAP (500 µM) significantly decreased cell viability. Pretreatment of the cells with antioxidants, 200 µM ascorbic acid and 100 µM tempol, completely reversed the effect of MS on the proteasome and cell viability. Conclusion Our results suggest for the first time that NSAIDs may have an implication in CVD through the direct inhibition of the proteasome system. Interestingly, this inhibitory effect of NSAIDs could be reversed by using antioxidants.

Dissipation of triclosan, triclocarban, carbamazepine and naproxen in agricultural soil following surface or sub-surface application of dewatered municipal biosolids

In many jurisdictions land application of municipal biosolids is a valued source of nutrients for crop production. The practice must be managed to ensure that crops and adjacent water are not subject to contamination by pharmaceuticals or other organic contaminants. The broad spectrum antimicrobial agents triclosan (TCS) and triclocarban (TCC), the anti-epileptic drug carbamazepine (CBZ), and the nonsteroidal anti-inflammatory drug naproxen (NAP) are widely used and are carried in biosolids. In the present study, the effect of biosolids and depth of placement in the soil profile on the rates of TCS, TCC, CBZ, and NAP dissipation were evaluated under semi-field conditions. Aggregates of dewatered municipal biosolids (DMBs) supplemented with 14C-labeled residues were applied either on the soil surface or in the subsurface of the soil profile, and incubated over several months under ambient outdoor conditions. The dissipation of TCS, TCC and NAP was significantly faster in sub-surface than surface applied biosolid aggregates. In contrast the dissipation rate for CBZ was the same in surface applied and incorporated aggregates. Overall, the present study has determined a significant effect of depth of placement on the dissipation rate of biodegradable molecules.

Chronic exposure to pollutants in Madín Reservoir (Mexico) alters oxidative stress status and flesh quality in the common carp Cyprinus carpio.

Madín Reservoir (MR) is located on the Río Tlalnepantla in Mexico. Previous studies seeking to identify pollutants at this site evidence that MR water contains a considerable metal load as well as nonsteroidal anti-inflammatory drugs (NSAIDs) at concentrations above those determined suitable for aquatic life. This study aimed to evaluate whether chronic exposure to pollutants in MR alters oxidative stress status and flesh quality in muscle of the common carp Cyprinus carpio. The following biomarkers were evaluated in muscle of carp caught in the general area of discharge from the town of Viejo Madín: hydroperoxide content (HPC), lipid peroxidation (LPX), protein carbonyl content (PCC), and activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Physicochemical and textural properties of muscle were also evaluated. Results show that the metals Al and Fe were accumulated in muscle of C. carpio at levels of 21.3 and 29.6 μg L(-1), respectively, and the NSAIDs diclofenac, ibuprofen, and naproxen at levels from 0.08 to 0.21 ng L(-1). Fish exposed to discharge from the town of Viejo Madín showed significant increases in HPC (9.77 %), LPX (69.33 %), and PCC (220 %) with respect to control specimens (p < 0.05). Similarly, enzyme activity increased significantly: SOD (80.82 %), CAT (98.03 %), and GPx (49.76 %). In muscle, physicochemical properties evidenced mainly significant reductions compared to control values while textural properties showed significant increases. Thus, water in this reservoir is contaminated with xenobiotics that alter some biological functions in C. carpio, a fish species consumed by the local human population.

Determination of pharmaceutical compounds in sewage sludge using a standard addition method approach

An analytical method for the simultaneous determination of eight pharmaceutical compounds in biosolids from urban wastewater treatment plants (WWTPs) was developed and validated. The compounds evaluated were non-steroidal anti-inflammatory drugs (naproxen, diclofenac, and ibuprofen), lipid regulators (clofibric acid), and antibiotics (sulfathiazole, sulfapyridine, sulfamethazine, and sulfamethoxazole). Ultrasound assisted extraction with a water–methanol solvent mixture (1:1, v:v) was performed and the compounds were then determined by liquid chromatography coupled with tandem mass spectrometry. The design of the method was based on the application of the standard addition calibration methodology to reduce matrix interferences. Validation procedures were conducted with rabbit excrements as blank samples. Recoveries of the target analytes ranged from 76 to 131% in spiked samples at 50, 200 or 1000 ng g−1 dry weight (dw). The relative standard deviations were in the range of 5–15% and the method detection limits ranged from 2 to 12 ng g−1dw. The method was applied to monitor pharmaceutical concentrations in biosolids from different WWTPs over an eight-month period (May to December 2011). Diclofenac, sulfapyridine and ibuprofen were detected in most of the samples whereas sulfamethazine and ibuprofen were the pharmaceuticals found in the highest concentrations (>200 ng g−1 dw on average).

Selective and simultaneous determination of NSAIDs in equine plasma by HPLC with molecularly imprinted solid-phase extraction.

Detection of nonsteroidal anti-inflammatory drugs (NSAIDs) in equine plasma is a significant analytical problem in veterinary anti-doping controls. A new HPLC method coupled to selective extraction with molecularly imprinted polymers was developed for the simultaneous determination in equine plasma of the NSAIDs phenylbutazone, flunixin, oxyphenbutazone, ketoprofen and naproxen. The analytical performances of the method have been evaluated both in standard solutions and equine plasma samples. Recovery: Molecularly imprinted polymers solid-phase extraction for all NSAIDs was >94% with intra-day values below 15.0% and inter-day values below 20%. Method quantification limit was 0.01 μg/ml. The developed method could be considered as a useful alternative to existing screening methods for the determination of NSAIDs in the context of studies of pharmacokinetics and anti-doping controls.

Neutrophil migration towards C5a and CXCL8 is prevented by non‐steroidal anti‐inflammatory drugs via inhibition of different pathways

Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to induce PG-independent anti-inflammatory actions. Here, we investigated the role of three different NSAIDs (naproxen, ibuprofen and oxaprozin) on neutrophil responses to CXCL8 and C5a. Human neutrophils were isolated from healthy volunteers by dextran and Ficoll-Hypaque density gradients. Neutrophils were pre-incubated with different concentrations (1-100 µM) of NSAIDs or kinase inhibitors. Neutrophil degranulation into supernatants was tested by elisa and zymography. Neutrophil chemotaxis was determined using Boyden chambers. F-actin polymerization was determined by Alexa-Fluor 488-conjugated phalloidin fluorescent assay. Integrin expression was assessed by flow cytometry. The phosphorylation of intracellular kinases was studied by Western blot. Pretreatment with NSAIDs did not affect neutrophil degranulation, but inhibited neutrophil migration and polymerization of F-actin, in response to CXCL8 and C5a. Pretreatment with different NSAIDs prevented C5a-induced integrin (CD11b) up-regulation, while only ibuprofen reduced CXCL8-induced CD11b up-regulation. Pre-incubation with naproxen or oxaprozin, but not ibuprofen, inhibited the PI3K/Akt-dependent chemotactic pathways. Both endogenous (released in cell supernatants) or exogenous (added to cell cultures) PGE2 did not affect C5a- or CXCL8-induced activities. Short-term incubation with NSAIDs did not affect neutrophil PGE2 release. Treatment with NSAIDs reduced C5a- and CXCL8-induced neutrophil migration and F-actin polymerization via different mechanisms. Inhibition by ibuprofen was associated with integrin down-regulation, while naproxen and oxaprozin blocked the PI3K/Akt pathway. Both NSAID actions were independent of COX inhibition and PGE2 release.

ChemInform Abstract: Pharmaceutical Salts and Cocrystals Involving Amino Acids: A Brief Structural Overview of the State‐of‐Art

AbstractReview: 160 refs.

Anti-inflammatory drugs interacting with Zn (II) metal ion based on thiocyanate and azide ligands: Synthesis, spectroscopic studies, DFT calculations and antibacterial assays

Zinc (II) complexes with non-steroidal anti-inflammatory drugs (NSAIDs) naproxen (nap) and ibuprofen (ibu) were synthesized in the presence of nitrogen donor ligands (thiocyanate or azide). The complexes were characterized by elemental analysis, FT-IR, 1H NMR and UV–Vis spectroscopes. The binding modes of the ligands in complexes were established by means of molecular modeling of the complexes, and calculation of their IR, NMR and absorption spectra at DFT (TDDFT)/B3LYP level were studied. The experimental and calculated data verified monodentate binding through the carboxylic oxygen atoms of anti-inflammatory drugs in the zinc complexes. The calculated 1H, FT-IR and UV–Vis data are in better agreement with the experimental results, and confirm the predicted tetrahedral structures for the Zn (II) complexes. In addition to DFT calculations of complexes, natural bond orbital (NBO) was performed at B3LYP/6-31+G(d,p) level of theory. Biological studies showed the antibacterial activity of zinc complexes against Gram-positive and Gram-negative bacterial strains.

Polymer–naproxen precipitation by supercritical antisolvent (SAS) process

The non-steroidal anti-inflammatory drug naproxen (NAP) has been coprecipitated with two different biopolymers, Eudragit (EUD) and poly(l-lactic acid) (PLA), by a supercritical antisolvent process (SAS). NAP release profiles were determined in simulated gastric and intestinal fluids in order to identify the best polymer to use for different administration routes. The in vitro release profiles of the NAP–EUD and NAP–PLA systems showed a slower and more controlled release in comparison to the untreated NAP. Moreover, the effects of pressure, temperature, initial concentration of the solution and drug-to-polymer ratio on the particle size and morphology of these drug-polymer systems have been evaluated. Although the morphology was spherical for both kinds of system, the NAP–PLA particles are larger than the NAP–EUD particles. A larger particle size is also obtained on using a lower pressure. However, the temperature did not influence, or only had a slight influence on, the particle size of NAP–PLA systems but it did have an influence on NAP–EUD systems.

CP-026 Implementation of quality prescribing indicators and compliance by a Rheumatology Team

BackgroundThe Andalusian Public Health Care Service have developed some indicators based on the selection of drugs for which there is better evidence of efficiency within several therapeutic groups, in areas...

Preventive Effects of NSAIDs, NO-NSAIDs, and NSAIDs Plus Difluoromethylornithine in a Chemically Induced Urinary Bladder Cancer Model

Urinary bladder cancer prevention studies were performed with the nonsteroidal anti-inflammatory drugs (NSAID) naproxen (a standard NSAID with a good cardiovascular profile), sulindac, and their nitric oxide (NO) derivatives. In addition, the effects of the ornithine decarboxylase inhibitor, difluoromethylornithine (DFMO), alone or combined with a suboptimal dose of naproxen or sulindac was examined. Agents were evaluated at their human equivalent doses (HED), as well as at lower doses. In the hydroxybutyl(butyl)nitrosamine (OH-BBN) model of urinary bladder cancer, naproxen (400 or 75 ppm) and sulindac (400 ppm) reduced the incidence of large bladder cancers by 82%, 68%, and 44%, respectively, when the agents were initially given 3 months after the final dose of the carcinogen; microscopic cancers already existed. NO-naproxen was highly effective, whereas NO-sulindac was inactive. To further compare naproxen and NO-naproxen, we examined their effects on gene expression in rat livers following a 7-day exposure. Limited, but similar, gene expression changes in the liver were induced by both agents, implying that the primary effects of both are mediated by the parent NSAID. When agents were initiated 2 weeks after the last administration of OH-BBN, DFMO at 1,000 ppm had limited activity, a low dose of naproxen (75 ppm) and sulindac (150 ppm) were highly and marginally effective. Combining DFMO with suboptimal doses of naproxen had minimal effects, whereas the combination of DMFO and sulindac was more active than either agent alone. Thus, naproxen and NO-naproxen were highly effective, whereas sulindac was moderately effective in the OH-BBN model at their HEDs.

Pharmaceutical salts and cocrystals involving amino acids: A brief structural overview of the state-of-art

Salification of new drug substances in order to improve physico-chemical or solid-state properties (e.g. dissolution rate or solubility, appropriate workup process, storage for further industrial and marketing development) is a well-accepted procedure. Amino acids, like aspartic acid, lysine or arginine take a great part in this process and are implicated in several different formulations of therapeutic agent families, including antibiotics (amoxicillin from beta lactam class or cephalexin from cephalosporin class), NSAIDs (ketoprofen, ibuprofen and naproxen from profen family, acetylsalicylic acid) or antiarrhythmic agents (e.g. ajmaline). Even if more than a half of known pharmaceutical molecules possess a salifiable moiety, what can be done for new potential drug entity that cannot be improved by transformation into a salt? In this context, after a brief review of pharmaceutical salts on the market and the implication of amino acids in these formulations, we focus on the advantage of using amino acids even when the target compound is not salifiable by exploiting their zwitterionic potentialities for cocrystal edification. We summarize here a series of new examples coming from literature to support the advantages of broadening the application of amino acids in formulation for new drug substances improvement research for non-salifiable molecules.

Effects of Some Non Steroidal Anti-inflammatory Drugs on Ovulation in Women with Mild Musculoskeletal Pain (A Clinical Study)

NSAIDs are popular drugs used for variable conditions, being analgesics, antipyretics and anti- inflammatory agents for more than a century. They are sold without a prescription and taken by millions of patients every day all over the world. Since they are used on a large scale as an anti-inflammatory agents & are given in doses that are consider high as compared to doses used in conditions other than inflammation and because many of NSAIDs users are females at child bearing age, so the present study was conducted to investigate the effects of diclofenac, naproxen & etoricoxib on ovulation & progesterone level in women. Adults women (39 females at fertile age ) were chosen as volunteers to take part in this study. They were visited the Rheumatology consultation clinic in Baghdad Hospital, suffering from minor aches & were diagnosed & received one of the three test drugs included in this study ( diclofenac 100mg once daily, naproxen500mg twice daily & etoricoxib 90mg once daily). Treatment with the above drugs was lasted for ten days starting at day ten after the onset of the period, a blood sample was taken from each patients for hormonal analysis( progesterone level) together with an ultra sonsography(U/S) to assess the mean diameter of the dominant follicle. At day twenty the patient came back for another ultra sonography & to give a blood sample for another check for progesterone level. A fourth group served as controls, who received no treatment ( volunteers ). The present study presents several new findings: 1. A significant inhibition of ovulation have been observed in patients teated with diclofenac , naproxen & etoricoxib. 2. Diclofenac was the highest inhibitor of ovulation compared to the other two drugs ( naproxen & etoricoxib ). 3. A significant decrease in progesterone level in all three groups in compared to the control group. 4. Functional cysts have been observed in one third of patients by the end of the treatment period with diclofenac, naproxen & etoricoxib due to unruptured follicles ( disappeared at the next cycle ). The above new findings have a direct implication & importance in relation to conditions where NSAIDs ( diclofenac, naproxen & eroricoxib ) used and may serve as an alarm of the harmful effects of these drugs on female fertility & these effects should be taken into consideration in females planning to have a child. In the other hand, the above results may open the door for looking for an emergency contraceptive tablet safer than those at use nowadays.

THREE CARDINAL LESSONS FROM ADAPT – 10 YEARS ON

The Alzheimer's Disease Anti-inflammatory Prevention Trial was a placebo-controlled three-arm pharmaco-prevention trial of the non-steroidal anti-inflammatory drugs naproxen sodium and celecoxib for prevention of incident Alzheimer's disease (AD) dementia in older (aged 70 and over) adults. Although subjects were at increased risk of symptoms because of a firstdegree family history, they were meant to be cognitively healthy at enrollment. ADAPT encountered several problems that resulted in the termination of its treatments after only two years on average. Interim results were complex but potentially interesting. In the end, however, the results were null. We describe the complications that prevented ADAPT from achieving conclusive results, and suggest that these could have been avoided if the trial design and execution had been better guided by preliminary data. We believe such data should be available before beginning further ambitious phase III trials of this sort, and we suggest a broad method by which such data can be accumulated with reasonable economy.

Novel metallo-therapeutics of the NSAID naproxen. Interaction with intracellular components that leads the cells to apoptosis

Two new mixed ligand-silver(I) complexes of the anti-inflammatory drug naproxen (naprH) and triphenylphosphine (tpp) or tri(p-tolyl)phosphine (tptp) of formulae {[Ag(tpp)3(napr)](H2O)} (1) and [Ag(tptp)2(napr)] (2) have been synthesized and characterized by m.p., vibrational spectroscopy (mid-FT-IR), Raman, (1)H-NMR, UV-Vis, ESI-MS spectroscopic techniques and X-ray crystallography. The complexes show high photo-sensitivity to UVC light. Photolysis of 1-2 was studied and the results showed monotonic degradation of the complexes with simultaneous triarylphosphine oxide formation. The complexes 1-2 were tested for their antiproliferative activity against human breast adenocarcinoma (MCF-7) cells. Complexes 1-2 were more active than cisplatin against cells. UVC light increases the effectiveness of complexes 1-2 on MCF-7 cells by 13% and 38% respectively. Due to the morphology of the MCF-7 cells, which were incubated with the complexes 1-2, the cell death was ascribed to apoptosis. Electrophoresis to genomic DNA of MCF-7 cells confirmed the apoptosis through DNA fragmentation. The binding affinity of 1-2 towards the intracellular molecules CT-DNA and lipoxygenase (LOX) was studied for the evaluation of the mechanism of cell death. Thus, the binding constants (K(b)) of 1-2 towards CT-DNA calculated by UV-Vis spectra are 32.8 ± 8.5 × 10(4) (1) and 4.7 ± 1.8 × 10(4) (2) M(-1), respectively. Changes in fluorescent emission light of ethidium bromide (EB) in the presence of DNA suggest intercalation or electrostatic interactions into DNA of both complexes 1-2 in the minor groove. The corresponding apparent binding constants (K(app)) of 1-2 towards CT-DNA calculated through fluorescence spectra are 2.9 ± 0.3 × 10(4) (1) and 1.6 ± 0.4 × 10(4) (2) M(-1) respectively. Docking studies on DNA-complexes interactions show the binding of 1 in the major groove and the corresponding one of 2 in the minor one. Moreover, the influence of complexes 1-2 on the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically and theoretically studied. Only 1 inhibits lipoxygenase activity (IC50 = 5.1 (1), >30 (2) μM).