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1.
Environ Sci Pollut Res Int ; 31(26): 38298-38309, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38797755

ABSTRACT

Thiosulfate gold leaching is one of the most promising green cyanide-free gold extraction processes; however, the difficulty of recovering Au(I) from the leaching system hinders its further development. This study prepared aminoguanidine-functionalized microspheres (AGMs) via a one-step reaction involving nucleophilic substitution between aminoguanidine hydrochloride and chloromethylated polystyrene microspheres and used AGMs to adsorb Au(I) from thiosulfate solutions. Scanning electron microscopy, Brunauer-Emmett-Teller analysis, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy were used to analyze the structure and properties of AGMs. Experiments were designed to investigate the effects of pH, temperature, initial Au(I), and thiosulfate concentrations on the gold adsorption performance of AGMs. Results demonstrated that AGMs can efficiently adsorb Au(I) from thiosulfate solutions in a wide pH range. The adsorption process conforms to the pseudo-second-order kinetic model and Langmuir isotherm model, with a maximum capacity of 22.03 kg/t. Acidic thiourea is an effective desorbent, and after four adsorption-desorption cycles, the adsorption rate of Au(I) by AGMs is 78.63%, which shows AGMs have good cyclic application potential. Based on the results of characterization, experiments, and density functional theory calculations, the mechanism for the adsorption of [Au(S2O3)2]3- on AGMs involves anion exchange. Importantly, AGMs exhibited satisfactory adsorption property for Au(I) in practical Cu2+-NH3(en)-S2O32- systems. This study provided experimental reference for the recovery of Au(I) from thiosulfate solution.


Subject(s)
Gold , Guanidines , Thiosulfates , Thiosulfates/chemistry , Adsorption , Guanidines/chemistry , Gold/chemistry , Kinetics , Spectroscopy, Fourier Transform Infrared , Hydrogen-Ion Concentration , Microspheres
2.
Int J Biol Macromol ; 270(Pt 1): 132193, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38723816

ABSTRACT

Developing a sorbent for the removal of La3+ ions from wastewater offers significant environmental and economic advantages. This study employed an ion-imprinting process to integrate La3+ ions into a newly developed derivative of aminoguanidine-chitosan (AGCS), synthesized via an innovative method. The process initiated with the modification of chitosan by attaching cyanoacetyl groups through amide bonds, yielding cyanoacetyl chitosan (CAC). This derivative underwent further modification with aminoguanidine to produce the chelating AGCS biopolymer. The binding of La3+ ions to AGCS occurred through imprinting and cross-linking with epichlorohydrin (ECH), followed by the extraction of La3+, resulting in the La3+ ion-imprinted sorbent (La-AGCS). Structural confirmation of these chitosan derivatives was established through elemental analysis, FTIR, and NMR. SEM analysis revealed that La-AGCS exhibited a more porous structure compared to the smoother non-imprinted polymer (NIP). La-AGCS demonstrated superior La3+ capture capability, with a maximum capacity of 286 ± 1 mg/g. The adsorption process, fitting the Langmuir and pseudo-second-order models, indicated a primary chemisorption mechanism. Moreover, La-AGCS displayed excellent selectivity for La3+, exhibiting selectivity coefficients ranging from 4 to 13 against other metals. This study underscores a strategic approach in designing advanced materials tailored for La3+ removal, capitalizing on specific chelator properties and ion-imprinting technology.


Subject(s)
Chitosan , Guanidines , Lanthanum , Molecular Imprinting , Wastewater , Water Pollutants, Chemical , Chitosan/chemistry , Lanthanum/chemistry , Wastewater/chemistry , Adsorption , Guanidines/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/analysis , Molecular Imprinting/methods , Water Purification/methods , Ions , Kinetics
3.
Int J Parasitol Drugs Drug Resist ; 25: 100546, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38733883

ABSTRACT

Schistosomiasis caused by Schistosoma spp. is a disease that causes a considerable health burden to millions of people worldwide. The limited availability of effective drugs on the market and the increased risk of resistance development due to extensive usage, highlight the urgent need for new antischistosomal drugs. Recent studies have shown that robenidine derivatives, containing an aminoguanidine core, exhibit promising activities against Plasmodium falciparum, motivating further investigation into their efficacy against Schistosoma mansoni, due to their similar habitat and the resulting related cellular mechanisms like the heme detoxification pathway. The conducted phenotypic screening of robenidine and 80 derivatives against newly transformed schistosomula and adult Schistosoma mansoni yielded 11 candidates with low EC50 values for newly transformed schistosomula (1.12-4.63 µM) and adults (2.78-9.47 µM). The structure-activity relationship revealed that electron-withdrawing groups at the phenyl moiety, as well as the presence of methyl groups adjacent to the guanidine moiety, enhanced the activity of derivatives against both stages of Schistosoma mansoni. The two compounds 2,2'-Bis[(3-cyano-4-fluorophenyl)methylene] carbonimidic Dihydrazide Hydrochloride (1) and 2,2'-Bis[(4-difluoromethoxyphenyl) ethylidene] carbonimidic Dihydrazide Hydrochloride (19), were selected for an in vivo study in Schistosoma mansoni-infected mice based on their potency, cytotoxicity, pharmacokinetic-, and physicochemical properties, but failed to reduce the worm burden significantly (worm burden reduction <20%). Thus, robenidine derivatives require further refinements to obtain higher antischistosomal specificity and in vivo activity.

4.
Article in English | MEDLINE | ID: mdl-38662416

ABSTRACT

Electron-beam-evaporated nickel oxide (NiOx) films are known for their high quality, precise control, and suitability for complex structures in perovskite (PVK) solar cells (PSCs). However, untreated NiOx films have inherent challenges, such as surface defects, relatively low intrinsic conductivity, and shallow valence band maximum, which seriously restrict the efficiency and stability of the devices. To address these challenges, we employ a dual coordination optimization strategy. The strategy includes low heating rate annealing of NiOx films and using an aminoguanidine nitrate spin coating process on the surfaces of NiOx films to strategically modify NiOx films itself and the interface of NiOx/PVK. Under the synergistic effect of this dual optimization method, the quality of the films is significantly improved and its p-type characteristics are enhanced. At the same time, the interface defects and energy level alignment of the films are effectively improved, and the charge extraction ability at the interface is improved. The combined treatment significantly improved the efficiency of inverted PSCs, from 17.85% to 20.31%, and enhanced device stability under various conditions. This innovative dual-coordinated optimization strategy provides a clear and effective framework for improving the performance of NiOx films and inverted PSCs.

5.
Arch Oral Biol ; 161: 105937, 2024 May.
Article in English | MEDLINE | ID: mdl-38442471

ABSTRACT

OBJECTIVE: To evaluate the role of induced nitric oxide synthase (iNOS) in nociception/orofacial discomfort in rats submitted to tooth whitening with hydrogen peroxide (H2O2). DESIGN: Wistar rats were divided into three groups (n = 24/group): a sham group not submitted to whitening treatment, a saline group submitted to whitening treatment, and a test group submitted to whitening treatment and blockade of iNOS with aminoguanidine 50 mg/kg/day. After 24 and 48 h, and 7 days, the animals were euthanized to collect trigeminal ganglia and maxillae to histomorphometric analysis (size of neuronal bodies and percentage of pulp area filled by vessels) and behavior/nociception (Grimace scales, scratching and biting counting, weight loss and nociception assay). ANOVA-1- or - 2-way tests were used (p < 0.05, GraphPadPrism 5.0). RESULTS: The aminoguanidine-treated group showed a reduction in nociceptive threshold in the masseteric region (p < 0.001), Grimace scale scores (p < 0.001), number of scratching (p = 0.011) and body mass loss (p = 0.007). After 24 and 48 h of tooth bleaching, the saline group showed a significant increase in the mean area of the blood vessels (p = 0.020) and iNOS immunostaining in odontoblasts (p = 0.002) and non-odontoblasts cells (p = 0.025). Aminoguanidine reversed both increases. Tooth bleaching reduced the mean area of neuronal bodies, and aminoguanidine significantly reversed it (p = 0.019), but an increase in GFAP immunostaining in neuronal bodies did not reduce after seven-days or after aminoguanidine treatment (p = 0.003). CONCLUSION: iNOS blockage by aminoguanidine plays an important role in nociception and orofacial discomfort by control of inflammation in dental pulp after tooth bleaching with hydrogen peroxide (H2O2) 35%.


Subject(s)
Guanidines , Tooth Bleaching Agents , Tooth Bleaching , Rats , Animals , Hydrogen Peroxide/pharmacology , Nociception , Nitric Oxide , Rats, Wistar , Nitric Oxide Synthase
6.
Poult Sci ; 103(4): 103484, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38306918

ABSTRACT

Goose astrovirus (GAstV)-2, a novel pathogen identified in 2018, mainly causes visceral gout in goslings, leading to approximately 50% mortality. At present, no commercial veterinary products are available to prevent and treat the disease. Our previous studies showed that nitric oxide (NO) and inducible NO synthase (iNOS) were markedly higher in the kidney and spleen of goslings infected with GAstV-2, but their effects during GAstV-2 infection remain unclear. In the present study, goslings were intraperitoneally injected with aminoguanidine (AG)-an iNOS inhibitor-to examine the role of NO during GAstV-2 infection. AG significantly decreased the serum NO concentration and iNOS mRNA expression in the kidney. Moreover, AG reduced the mortality, serum uric acid and creatinine content, and urate deposition in visceral organs and joints. Histopathological analysis demonstrated that AG reduced renal tubular cell necrosis, inflammatory cell infiltration, glycogen deposition in glomerular mesangium, and interstitial fibrosis, suggesting alleviation of kidney lesions. Furthermore, AG decreased the expression of renal injury markers such as KIM-1 and desmin; inflammatory cytokine-related genes such as IL-1ß, IL-8, and MMP-9; and autophagy-related genes and proteins such as LC3II, ATG5, and Beclin1. However, quantitative real-time PCR and immunohistochemistry showed that treatment with AG did not affect the kidney and liver viral load. These findings suggest that AG decreases the mortality rate and kidney lesions in goslings infected with GAstV-2 through mechanisms associated with autophagy and inhibition of inflammatory cytokine production in the kidney but not with GAstV-2 replication.


Subject(s)
Astroviridae Infections , Astroviridae , Avastrovirus , Gout , Guanidines , Animals , Geese , Uric Acid , Chickens , Astroviridae/genetics , Gout/drug therapy , Gout/veterinary , Astroviridae Infections/drug therapy , Astroviridae Infections/veterinary , Kidney/pathology , Cytokines , Avastrovirus/genetics
7.
J Fluoresc ; 2023 Nov 16.
Article in English | MEDLINE | ID: mdl-37971607

ABSTRACT

Carnosine is beta-alanyl histidine, a dipeptide, endogenously produced in our body by the carnosine synthase enzyme. It is an antioxidant, thus protecting from the deleterious effect of advanced glycation end products (AGEs). Similarly, aminoguanidine (AG) also prevents AGEs formation by scavenging free radicals such as reactive oxygen species (ROS)/reactive carbonyl species (RCS). This study used experimental and computational techniques to perform a comparative analysis of carnosine and AG and their inhibiting properties against glycated human serum albumin (HSA). Fructose-mediated glycation of albumin produced fluorescent structures, such as pentosidine and malondialdehyde. These AGEs were significantly reduced by carnosine and AG. At 20 mM, carnosine and AG quenches pentosidine fluorescence by 66% and 83%, respectively. A similar inhibitory effect was observed for malondialdehyde. Protein hydrophobicity and tryptophan fluorescence were restored in the presence of carnosine and AG. Aminoguanidine decreased fibrillation in HSA, while carnosine did not significantly affect aggregation/fibrillation. In addition, molecular docking study observed binding scores of -5.90 kcal/mol and -2.59 kcal/mol by HSA-aminoguanidine and HSA-carnosine complex, respectively. Aminoguanidine forms one conventional hydrogen bond with ARG A:10 and a salt bridge with ASP A:13, ASP A:259, ASP A:255, and ASP A:256 from the amine group. Similarly, carnosine forms only hydrogen bonds with GLU A:501 and GLN A:508 from the amine and hydroxy group. The root mean square deviation (RMSD) calculated from simulation studies was 1 nm upto 70 ns for the HSA-aminoguanidine complex and the spectrum of HSA-carnosine was significantly deviated and not stabilized. The superior inhibitory activity of aminoguanidine could be due to additional salt bridge bonding with albumin. Conclusively, aminoguanidine can be the better treatment choice for diabetes-associated neurological diseases.

8.
Int J Mol Sci ; 24(19)2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37834192

ABSTRACT

Pyridoxylidene-aminoguanidine (PLAG) and its transition metal complexes are biologically active compounds with interesting properties. In this contribution, three new metal-PLAG complexes, Zn(PLAG)(SO4)(H2O)].∙H2O (Zn-PLAG), [Co(PLAG)2]SO4∙2H2O (Co-PLAG), and [Fe(PLAG)2]SO4∙2H2O) (Fe-PLAG), were synthetized and characterized by the X-ray crystallography. The intermolecular interactions governing the stability of crystal structure were compared to those of Cu(PLAG)(NCS)2 (Cu-PLAG) within Hirshfeld surface analysis. The structures were optimized at B3LYP/6-31+G(d,p)(H,C,N,O,S)/LanL2DZ (Fe,Co,Zn,Cu), and stability was assessed through Natural Bond Orbital Theory and Quantum Theory of Atoms in Molecules. Special emphasis was put on investigating the ligand's stability and reactivity. The binding of these compounds to Bovine and Human serum albumin was investigated by spectrofluorometric titration. The importance of complex geometry and various ligands for protein binding was shown. These results were complemented by the molecular docking study to elucidate the most important interactions. The thermodynamic parameters of the binding process were determined. The binding to DNA, as one of the main pathways in the cell death cycle, was analyzed by molecular docking. The cytotoxicity was determined towards HCT116, A375, MCF-7, and A2780 cell lines. The most active compound was Cu-PLAG due to the presence of PLAG and two thiocyanate ligands.


Subject(s)
Coordination Complexes , Ovarian Neoplasms , Female , Animals , Cattle , Humans , Protein Binding , Cell Line, Tumor , Molecular Docking Simulation , Metals , DNA/chemistry , Coordination Complexes/chemistry , Zinc/chemistry , Ligands , Copper/chemistry
9.
Cureus ; 15(7): e42426, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37637592

ABSTRACT

BACKGROUND/AIM: Diabetes is a multifactorial syndrome that affects the functioning of the renin-angiotensin system (RAS). The role of advanced glycation end products (AGEs) in diabetes is well known. In the present study, we hypothesized that the prevention of AGE accumulation or abrogation of AGE synthesis using an AGE inhibitor, aminoguanidine (AG), in streptozotocin (STZ)-induced diabetic animal models would affect the progression of diabetes and its related complications. We determined the effects of aminoguanidine (AG), an AGE inhibitor, in STZ-induced diabetic rats by determining various indices of RAS and renal functions. Additionally, we also investigated the effect of the drug, AG, on various hemodynamic and physiological functions in the body of the animals. METHODS: Male Sprague Dawley rats weighing 200-250 g were assigned to four groups (n = 4-6): Vehicle, Vehicle+AG, STZ-induced, and STZ-induced+AG rats. Type 1 diabetes was induced by a single intraperitoneal (IP) injection of streptozotocin (55 mg/kg) dissolved in sodium citrate buffer. The control groups (Vehicle) were injected with buffer. The blood glucose levels were measured after 48 hours, and animals with blood glucose levels > 300 mg/dL were included in the study. Blood glucose levels in the vehicle rats were also determined to ensure non-diabetic conditions. After confirmation, AG was administrated at a dose of 1 g/L in drinking water for two weeks. Urine was collected to measure the glomerular filtration rate (GFR), and the immune reactivity for AT1 and AT2 proteins was analyzed by immunoblotting. Data were expressed as mean ± standard error of the mean (SEM), and a p-value < 0.05 was considered statistically significant. RESULTS: Diabetic rats had a significant drop in body weight, accompanied by increased food and water consumption. The diabetic rats exhibited significantly increased urine flow and GFR. These phenotypes were significantly or considerately reversed by AG treatment in the STZ+AG-treated diabetic rats. Aminoguanidine prevented the increase in blood sugar levels compared to STZ-induced diabetic rats alone (295.9 ± 50.69 versus 462.3 ± 18.6 mg/dL (p < 0.05)). However, it did not affect the glomerular filtration rate (GFR) and glomerular damage, as assessed by the renal histopathological studies. The STZ-induced diabetic rats had an increased sodium excretion (3.24 ± 0.40 mmol) and significantly increased expression of the AT2 receptor and that of the AT1 receptor, which was slightly reversed by the treatment with AG. Treatment with AG decreased sodium excretion (2.12 ± 0.63, as compared to the diabetic rats). These rats also had modestly decreased expression of the AT2 receptor (0.99 ± 0.07 versus 1.12 ± 0.08, as compared to the STZ-induced diabetic rats), while the AT1 receptors showed a slight increase in the STZ+AG-treated rats compared to the STZ-induced diabetic rats (1.1 ± 0.19 versus 1.08 ± 0.12). CONCLUSION: This study highlights the action of the drug AG in not exacerbating any damage in diabetic rats. Employing AG as a pharmacological intervention to prevent an increase in blood sugar adds a new dimension to controlling increased blood sugar and preventing diabetic complications. The employability and pharmacological intervention of the drug AG, in diabetes, therefore, need a renewed and further investigation.

10.
Antioxidants (Basel) ; 12(8)2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37627609

ABSTRACT

Polyamine (PA) catabolism mediated by amine oxidases is an important process involved in fine-tuning PA homeostasis and related mechanisms during salt stress. The significance of these amine oxidases in short-term responses to salt stress is, however, not well understood. In the present study, the effects of L-aminoguanidine (AG) on tomato roots treated with short-term salt stress induced by NaCl were studied. AG is usually used as a copper amine oxidase (CuAO or DAO) inhibitor. In our study, other alterations of PA catabolism, such as reduced polyamine oxidase (PAO), were also observed in AG-treated plants. Salt stress led to an increase in the reactive oxygen and nitrogen species in tomato root apices, evidenced by in situ fluorescent staining and an increase in free PA levels. Such alterations were alleviated by AG treatment, showing the possible antioxidant effect of AG in tomato roots exposed to salt stress. PA catabolic enzyme activities decreased, while the imbalance of hydrogen peroxide (H2O2), nitric oxide (NO), and hydrogen sulfide (H2S) concentrations displayed a dependence on stress intensity. These changes suggest that AG-mediated inhibition could dramatically rearrange PA catabolism and related reactive species backgrounds, especially the NO-related mechanisms. More studies are, however, needed to decipher the precise mode of action of AG in plants exposed to stress treatments.

11.
Cells ; 12(10)2023 05 17.
Article in English | MEDLINE | ID: mdl-37408249

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor prognosis. Gemcitabine is the first-line therapy for PDAC, but gemcitabine resistance is a major impediment to achieving satisfactory clinical outcomes. This study investigated whether methylglyoxal (MG), an oncometabolite spontaneously formed as a by-product of glycolysis, notably favors PDAC resistance to gemcitabine. We observed that human PDAC tumors expressing elevated levels of glycolytic enzymes together with high levels of glyoxalase 1 (GLO1), the major MG-detoxifying enzyme, present with a poor prognosis. Next, we showed that glycolysis and subsequent MG stress are triggered in PDAC cells rendered resistant to gemcitabine when compared with parental cells. In fact, acquired resistance, following short and long-term gemcitabine challenges, correlated with the upregulation of GLUT1, LDHA, GLO1, and the accumulation of MG protein adducts. We showed that MG-mediated activation of heat shock response is, at least in part, the molecular mechanism underlying survival in gemcitabine-treated PDAC cells. This novel adverse effect of gemcitabine, i.e., induction of MG stress and HSR activation, is efficiently reversed using potent MG scavengers such as metformin and aminoguanidine. We propose that the MG blockade could be exploited to resensitize resistant PDAC tumors and to improve patient outcomes using gemcitabine therapy.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Gemcitabine , Pyruvaldehyde , Deoxycytidine/pharmacology , Deoxycytidine/therapeutic use , Antimetabolites, Antineoplastic/pharmacology , Pancreatic Neoplasms/pathology , Carcinoma, Pancreatic Ductal/metabolism , Heat-Shock Response , Pancreatic Neoplasms
12.
J Control Release ; 357: 310-318, 2023 05.
Article in English | MEDLINE | ID: mdl-37019286

ABSTRACT

Dendritic cells (DCs), the primary antigen-presenting cells in the immune system, play a critical role in regulating tumor immune responses. However, the tumor immunosuppressive microenvironment severely impedes the process of antigen-presenting and DC maturation, thereby limiting the efficacy of cancer immunotherapy. In this work, a pH-responsive polymer nanocarrier (PAG) modified with aminoguanidine (AG) was constructed for the efficient delivery of bortezomib (BTZ) through bidentate hydrogen bonds and electrostatic adsorption formed between guanidine groups of PAG and boronic acid groups of BTZ. The obtained PAG/BTZ nanoparticles exhibited pH-responsive release of BTZ and AG in the acidic tumor microenvironment. On the one hand, BTZ induced potent immune activation by eliciting immunogenic cell death (ICD) and releasing damage-associated molecular patterns. On the other hand, the cationic AG significantly promoted antigen uptake by DCs and activated DC maturation. As a result, PAG/BTZ significantly stimulated tumoral infiltration of cytotoxic T lymphocytes (CTLs) and triggered robust antitumor immune responses. Thus, it showed potent antitumor efficacy when synergizing with an immune checkpoint-blocking antibody.


Subject(s)
Nanoparticles , Neoplasms , Humans , Bortezomib/pharmacology , Drug Carriers/chemistry , Guanidine , Neoplasms/drug therapy , Antigens , Immunity , Nanoparticles/chemistry , Immunotherapy , Cell Line, Tumor , Tumor Microenvironment
13.
Life (Basel) ; 13(3)2023 Mar 09.
Article in English | MEDLINE | ID: mdl-36983901

ABSTRACT

L-aminoguanidine (AG) is an inhibitor frequently used for investigating plant abiotic stress responses; however, its exact mode of action is not well understood. Many studies used this compound as a specific diamine oxidase inhibitor, whereas other studies used it for reducing nitric oxide (NO) production. Recent studies suggest its antiglycation effect; however, this remains elusive in plants. This review summarises our current knowledge about different targets of AG in plants. Our recommendation is to use AG as a modulator of polyamine-related mechanisms rather than a specific inhibitor. In the future overall investigation is needed to decipher the exact mechanisms of AG. More careful application of AG could give more insight into plant abiotic stress responses.

14.
Curr Org Synth ; 20(8): 890-896, 2023.
Article in English | MEDLINE | ID: mdl-36974410

ABSTRACT

BACKGROUND: A combination of paclitaxel with antineoplastic agents or paclitaxel alone was used clinically for the treatment of metastatic breast cancer. However, paclitaxel has poor water solubility and limited effect on some metastatic breast cancers. Hence, novel paclitaxel derivatives are in demand. In addition, the inducible nitric oxide synthase inhibitor, and aminoguanidine has a synergistic antitumor effect with chemotherapeutics. OBJECTIVE: This study aims to design and synthesize the paclitaxel-aminoguanidine conjugates. Upon cellular internalization, the novel paclitaxel-aminoguanidine conjugates could release paclitaxel and aminoguanidine with the aid of esterase and weak acids in cancer cells. METHODS: Paclitaxel-aminoguanidine conjugates were synthesized using click chemistry. The biological activity of paclitaxel-aminoguanidine conjugates was evaluated by MTT assay, determination of nitric oxide, analysis of apoptosis and cell cycle, and wound healing assay. RESULTS: Here, a novel paclitaxel-aminoguanidine conjugate was synthesized using click chemistry. Compared with paclitaxel, the water solubility of paclitaxel-aminoguanidine conjugates increased obviously. Upon cellular internalization, the novel paclitaxel-aminoguanidine conjugates released paclitaxel and aminoguanidine to synergistically inhibit the proliferation and metastasis of breast cancer cells with the aid of esterase and weak acids in cancer cells. The results of the MTT assay showed that compared with paclitaxel or the mixture of paclitaxel and aminoguanidine, the cytotoxicity of compound 4 against 4T1 cells was enhanced. As for apoptosis induced by these compounds, the paclitaxel-aminoguanidine conjugates also had a stronger ability to induce apoptosis than paclitaxel or the mixture of paclitaxel and aminoguanidine. The results of the scratch test showed that the anti-metastatic effect of the conjugate was the strongest among these tested compounds. CONCLUSION: These findings indicate that paclitaxel-aminoguanidine conjugate is a promising anticancer agent worthy of further study.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Humans , Female , Paclitaxel/pharmacology , Paclitaxel/chemistry , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Esterases , Water
15.
Appl Microbiol Biotechnol ; 107(5-6): 1765-1784, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36808279

ABSTRACT

The ADP-ribosyl transferase activity of P. aeruginosa PE24 moiety expressed by E. coli BL21 (DE3) was assessed on nitrobenzylidene aminoguanidine (NBAG) and in vitro cultured cancer cell lines. Gene encoding PE24 was isolated from P. aeruginosa isolates, cloned into pET22b( +) plasmid, and expressed in E. coli BL21 (DE3) under IPTG induction. Genetic recombination was confirmed by colony PCR, the appearance of insert post digestion of engineered construct, and protein electrophoresis using sodium dodecyl-sulfate polyacrylamide gel (SDS-PAGE). The chemical compound NBAG has been used to confirm PE24 extract ADP-ribosyl transferase action through UV spectroscopy, FTIR, c13-NMR, and HPLC before and after low-dose gamma irradiation (5, 10, 15, 24 Gy). The cytotoxicity of PE24 extract alone and in combination with paclitaxel and low-dose gamma radiation (both 5 Gy and one shot 24 Gy) was assessed on adherent cell lines HEPG2, MCF-7, A375, OEC, and Kasumi-1 cell suspension. Expressed PE24 moiety ADP-ribosylated NBAG as revealed by structural changes depicted by FTIR and NMR, and the surge of new peaks at different retention times from NBAG in HPLC chromatograms. Irradiating recombinant PE24 moiety was associated with a reduction in ADP-ribosylating activity. The PE24 extract IC50 values were < 10 µg/ml with an acceptable R2 value on cancer cell lines and acceptable cell viability at 10 µg/ml on normal OEC. Overall, the synergistic effects were observed upon combining PE24 extract with low-dose paclitaxel demonstrated by the reduction in IC50 whereas antagonistic effects and a rise in IC50 values were recorded after irradiation by low-dose gamma rays. KEY POINTS: • Recombinant PE24 moiety was successfully expressed and biochemically analyzed. • Low-dose gamma radiation and metal ions decreased the recombinant PE24 cytotoxic activity. • Synergism was observed upon combining recombinant PE24 with low-dose paclitaxel.


Subject(s)
ADP Ribose Transferases , Pseudomonas aeruginosa , ADP Ribose Transferases/chemistry , ADP Ribose Transferases/genetics , ADP Ribose Transferases/metabolism , Pseudomonas aeruginosa/genetics , Gamma Rays , Escherichia coli/genetics
16.
Biomed Pharmacother ; 156: 113918, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36411611

ABSTRACT

In this study, the hepatoprotective effect of aminoguanidine in acute liver damage caused by carbon tetrachloride-CCl4 at a dose of 1 mL/kg, i.p. was investigated in experimental rats. Ten days of preventive treatment with aminoguanidine before exposure to toxic CCl4, at a dose of 150 mg/kg, i.p., led to significant reduction in biochemical markers of acute liver injury-AST(p < 0.001), ALT (p < 0.01), SDH (p < 0.05) and reduction in pro-oxidative markers-H2O2 (p < 0.05), TOS (p < 0.01), TBARS, and LOOH (p < 0.001) in relation to rats treated only CCl4. Treatment with aminoguanidine resulted in a significant reduction in the consumption of antioxidant-GR (p < 0.01), GST, GPx, GSH (p < 0.001), and a decrease in pro-inflammatory-TNF-α (p < 0.01), IL-1ß, IL-6, NO and NGAL (p < 0.001) markers relative to animals exposed to CCl4 alone. Also, aminoguanidine pre-treatment leads to an increase in arginase activity (p < 0.001), and a decrease in citrulline concentration (p < 0.01), as well as polyamine catabolism enzyme activity-putrescin oxidase and spermine oxidase (p < 0.001) in comparison to the CCl4 group. Aminoguanidine led to a striking reduction of the necrotic field (p < 0.001), and a significant increase in the number of apoptotic hepatocytes (p < 0.001), as well as the proapoptotic markers-BAX and Caspase-3 (p < 0.05), compared to CCl4. The hepatoprotective mechanisms in CCl4 induce hepatotoxicity of aminoguanidine are based on the strong antioxidant effects, inhibition of pro-oxidative and pro-inflammatory mediators, as well as induction of damaged hepatocytes into apoptosis.


Subject(s)
Chemical and Drug Induced Liver Injury , Rats , Animals , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/prevention & control , Hydrogen Peroxide , Carbon Tetrachloride/toxicity , Antioxidants/metabolism
17.
Pharmaceuticals (Basel) ; 15(10)2022 Sep 30.
Article in English | MEDLINE | ID: mdl-36297331

ABSTRACT

Amidrazones are widely used in chemical synthesis, industry and agriculture. We compiled some of the most important findings on the biological activities of amidrazones described in the years 2010-2022. The data were obtained using the ScienceDirect, Reaxys and Google Scholar search engines with keywords (amidrazone, carbohydrazonamide, carboximidohydrazide, aminoguanidine) and structure strategies. Compounds with significant biological activities were included in the review. The described structures derived from amidrazones include: amidrazone derivatives; aminoguanidine derivatives; complexes obtained using amidrazones as ligands; and some cyclic compounds obtained from amidrazones and/or containing an amidrazone moiety in their structures. This review includes chapters based on compound activities, including: tuberculostatic, antibacterial, antifungal, antiparasitic, antiviral, anti-inflammatory, cytoprotective, and antitumor compounds, as well as furin and acetylocholinesterase inhibitors. Detailed information on the compounds tested in vivo, along the mechanisms of action and toxicity of the selected amidrazone derivatives, are described. We describe examples of compounds that have a chance of becoming drugs due to promising preclinical or clinical research, as well as old drugs with new therapeutic targets (repositioning) which have the potential to be used in the treatment of other diseases. The described examples prove that amidrazone derivatives are a potential source of new therapeutic substances and deserve further research.

18.
Biomaterials ; 289: 121782, 2022 10.
Article in English | MEDLINE | ID: mdl-36099713

ABSTRACT

Bioprosthetic heart valves (BHV) fabricated from heterograft tissue, such as glutaraldehyde pretreated bovine pericardium (BP), are the most frequently used heart valve replacements. BHV durability is limited by structural valve degeneration (SVD), mechanistically associated with calcification, advanced glycation end products (AGE), and serum protein infiltration. We investigated the hypothesis that anti-AGE agents, Aminoguanidine, Pyridoxamine [PYR], and N-Acetylcysteine could mitigate AGE-serum protein SVD mechanisms in vitro and in vivo, and that these agents could mitigate calcification or demonstrate anti-calcification interactions with BP pretreatment with ethanol. In vitro, each of these agents significantly inhibited AGE-serum protein infiltration in BP. However, in 28-day rat subdermal BP implants only orally administered PYR demonstrated significant inhibition of AGE and serum protein uptake. Furthermore, BP PYR preincubation of BP mitigated AGE-serum protein SVD mechanisms in vitro, and demonstrated mitigation of both AGE-serum protein uptake and reduced calcification in vivo in 28-day rat subdermal BP explants. Inhibition of BP calcification as well as inhibition of AGE-serum protein infiltration was observed in 28-day rat subdermal BP explants pretreated with ethanol followed by PYR preincubation. In conclusion, AGE-serum protein and calcification SVD pathophysiology are significantly mitigated by both PYR oral therapy and PYR and ethanol pretreatment of BP.


Subject(s)
Bioprosthesis , Calcinosis , Heart Valve Prosthesis , Acetylcysteine , Animals , Blood Proteins , Cattle , Ethanol/pharmacology , Glutaral , Glycation End Products, Advanced , Pyridoxamine , Rats
19.
Microorganisms ; 10(9)2022 Sep 15.
Article in English | MEDLINE | ID: mdl-36144449

ABSTRACT

Advanced glycation end products (AGEs), formed through the nonenzymatic reaction of reducing sugars with the side-chain amino groups of lysine or arginine of proteins, followed by further glycoxidation reactions under oxidative stress conditions, are involved in the onset and exacerbation of a variety of diseases, including diabetes, atherosclerosis, and Alzheimer's disease (AD) as well as in the secondary stages of traumatic brain injury (TBI). AGEs, in the form of intra- and interprotein crosslinks, deactivate various enzymes, exacerbating disease progression. The interactions of AGEs with the receptors for the AGEs (RAGE) also result in further downstream inflammatory cascade events. The overexpression of RAGE and the AGE-RAGE interactions are especially involved in cases of Alzheimer's disease and other neurodegenerative diseases, including TBI and amyotrophic lateral sclerosis (ALS). Maillard reactions are also observed in the gut bacterial species. The protein aggregates found in the bacterial species resemble those of AD and Parkinson's disease (PD), and AGE inhibitors increase the life span of the bacteria. Dietary AGEs alter the gut microbiota composition and elevate plasma glycosylation, thereby leading to systemic proinflammatory effects and endothelial dysfunction. There is emerging interest in developing AGE inhibitor and AGE breaker compounds to treat AGE-mediated pathologies, including diabetes and neurodegenerative diseases. Gut-microbiota-derived enzymes may also function as AGE-breaker biocatalysts. Thus, AGEs have a prominent role in the pathogenesis of various diseases, and the AGE inhibitor and AGE breaker approach may lead to novel therapeutic candidates.

20.
Environ Pollut ; 309: 119788, 2022 Sep 15.
Article in English | MEDLINE | ID: mdl-35843454

ABSTRACT

Nitroguanidine (NQ) is an emerging contaminant being used by the military as a constituent of new insensitive munitions. NQ is also used in rocket propellants, smokeless pyrotechnics, and vehicle restraint systems. Its uncontrolled transformation in the environment can generate toxic and potentially mutagenic products, posing hazards that need to be remediated. NQ transformation has only been investigated to a limited extent. Thus, it is crucial to expand the narrow spectrum of NQ remediation strategies and understand its transformation pathways and end products. Iron-based reactive minerals should be investigated for NQ treatment because they are successfully used in existing technologies, such as permeable reactive barriers, for treating a wide range of organic pollutants. This study tested the ability of micron-sized zero-valent iron (m-ZVI), mackinawite, and commercial FeS, to transform NQ under anoxic conditions. NQ transformation followed pseudo-first-order kinetics. The reaction rate constants decreased as follows: commercial FeS > mackinawite > m-ZVI. For the assessed minerals, the NQ transformation started with the reduction of the nitro group forming nitrosoguanidine (NsoQ). Then, aminoguanidine (AQ) was accumulated during the reaction of NQ with m-ZVI, accounting for 86% of the nitrogen mass recovery. When NQ was reacted with commercial FeS, 45% and 20% of nitrogen were recovered as AQ and guanidine, respectively, after 24 h. Nonetheless, NsoQ persisted, contributing to the N-balance. When mackinawite was present, NsoQ disappeared, but AQ was not detected, and guanidine accounted for 11% of the nitrogen recovery. AQ was ultimately transformed into cyanamide, whose dimerization triggered the formation of cyanoguanidine. Alternatively, NsoQ was transformed into guanidine, which reacted with cyanamide to form biguanide. This is the first report systematically investigating the NQ transformation by different iron-based reactive minerals. The evidence indicates that these minerals are attractive alternatives for developing NQ remediation strategies.


Subject(s)
Iron , Water Pollutants, Chemical , Cyanamide , Guanidines , Minerals , Nitrogen
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