An electrochemical, and surface studies of synthesized Gemini ionic liquid as corrosion inhibitor for carbon steel in petroleum field.

In this work, we study the efficiency of N1, N3-dibenzyl-N1, N1, N3, N3-tetramethylpropane-1,3-diaminium chloride, as anticorrosion. This compound exhibits potential as a prospective remedy to stop the deterioration of carbon steel caused by corrosion in 1.0 M HCl. The synthesis of this compound is described in a comprehensive manner, and its composition is supported by a range of precise analytical approaches such as elemental analysis, and mass spectroscopy. Based on the findings of the investigation, the synthesized Gemini ionic liquid demonstrates a robust capacity to slow down the rate at which the metal corrodes. The Prepared compound was evaluation by electrochemical and morphology study. Our results revealed that elevating the inhibitor concentration led to an augmentation in inhibition effectiveness, reaching up to 94.8% at 200 ppm of the synthesized compound at 298 K. It is crucial to emphasize that the recently prepared Gemini ionic liquid is consistent with the Langmuir adsorption model and function as a mixed inhibitor, participating in the physio-chemisorption process of adsorption.

Removal of Cu2+, Fe2+ and SO42- ions from industrial wastewater by ion exchange resins contained in a rotating perforated cylindrical basket of different heights.

The present study is concerned with the development of a new cylindrical basket filled with ion exchange resin. The performance of the reactor was examined by removing Cu2+, Fe2+ and SO42- ions from synthetic wastewater. Variables studied were the initial ion concentration in the solution, contact time, resin height inside the cylindrical basket and cylindrical basket rotational speed. Dimensionless analysis was used to obtain a mass transfer correlation for each of the mentioned ions suitable for scale up and design of the present reactor. The experimental results revealed that both the percentage and the rate of removal of (Cu2+, Fe2+ and SO42-) ions decrease as the initial ion concentration in the solution increases, while they increase as the contact time, rotational speed and (L/d) ratio increase. Both Langmuir's and Freundlich's adsorption isotherms were examined and it was found that Langmuir's adsorption isotherm gives a better fitting for the obtained data than Freundlich's. Regeneration ability was tested, which revealed the high resin efficiency upon operating several consequence cycles that could reach 4 cycles with a slight decrease in the removal efficiency.

Adsorption, thermodynamic, and quantum chemical investigations of an ionic liquid that inhibits corrosion of carbon steel in chloride solutions.

The purpose of this work lies in the use of ionic liquids as corrosion inhibitors due to the difficulty in some oil fields with the solubility of corrosion inhibitors and these materials can be miscible with water and thus provide a solution to such problems in the industry. The second purpose is concerned with the lower toxicity of these compounds compared with the most common corrosion inhibitors. The study covered the corrosion inhibition performance of the ionic liquid 1-butyl-3-methylimidazolium trifluoromethyl sulfonate ([BMIm]TfO) for carbon steel in 3.5% NaCl solutions. The study comprised electrochemical, adsorption, and quantum chemical investigations. The results manifested that [BMIm]TfO can be considered a promising corrosion inhibitor and the inhibition efficacy intensifies as the concentration rises. The observed inhibitive effect can be correlated to the adsorption of the ionic liquid species and the creation of protecting films on the surface. The mode of adsorption follows the Langmuir adsorption isotherm. The polarization results showed that the ionic liquid [BMIm]TfO functions as a mixed inhibitor. Reliance of the corrosion influence on the temperature in the existence and absence of [BMIm]TfO was demonstrated in the temperature range of 303-333 K using polarization data. Activation parameters were determined and discussed. The observed inhibition performance of [BMIm]TfO was correlated with the electronic properties of the ionic liquid using a quantum chemical study.

Development of Isatin-Based Schiff Bases Targeting VEGFR-2 Inhibition: Synthesis, Characterization, Antiproliferative Properties, and QSAR Studies.

Three sets of isatin-based Schiff bases were synthesized utilizing the molecular hybridization approach. Some of the synthesized Schiff bases show significant to moderate antiproliferative properties against MCF7 (breast), HCT116 (colon), and PaCa2 (pancreatic) cancer cell lines with potency compared to reference drugs 5-fluorouracil (5-FU) and Sunitinib. Among all, compound 17 f (3-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)imino)-1-((1-(2-methoxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-methylindolin-2-one) exhibits promising antiproliferative properties against the MCF7 cancer cell line with 2.1-fold more potency than Sunitinib. However, among all the synthesized compounds, three (5-methylisatin derivatives) were the most effective against HCT116 in comparison to 5-FU. Compound 17 f exhibited the highest anti-angiogenic effect on the vasculature as it significantly reduced BV from 43 mm to 2 mm in comparison to 5.7 mm for Sunitinib and flow cytometry supports the arrest of the cell cycle at G1/S phases. In addition, compound 17 f also showed high VEGFR-2 inhibition properties against breast cancer cell lines. Robust 2D-QSAR studies supported the biological data.

Novel Sunifiram-carbamate hybrids as potential dual acetylcholinesterase inhibitor and NMDAR co-agonist: simulation-guided analogue design and pharmacological screening.

An efficient method for synthesising NMDAR co-agonist Sunifiram (DM235), in addition to Sunifram-carbamate and anthranilamide hybrids, has been developed in high yields via protecting group-free stepwise unsymmetric diacylation of piperazine using N-acylbenzotiazole. Compounds 3f, 3d, and 3i exhibited promising nootropic activity by enhancing acetylecholine (ACh) release in A549 cell line. Moreover, the carbamate hybrid 3f was found to exhibit higher in vitro potency than donepezil with IC50 = 18 ± 0.2 nM, 29.9 ± 0.15 nM for 3f and donepezil, respectively. 3f was also found to effectively inhibit AChE activity in rat brain (AChE = 1.266 ng/mL) compared to tacrine (AChE = 1.137 ng/ml). An assessment of the ADMET properties revealed that compounds 3f, 3d, and 3i are drug-like and can penetrate blood-brain barrier. Findings presented here showcase highly potential cholinergic agents, with expected partial agonist activity towards glycine binding pocket of NMDAR which could lead to development and optimisation of novel nootropic drugs.

New quinoline-triazole conjugates: Synthesis, and antiviral properties against SARS-CoV-2.

At present therapeutic options for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are very limited. We designed and synthesized three sets of small molecules using quinoline scaffolds. A series of quinoline conjugates (10a-l, 11a-c, and 12a-e) by incorporating 1,2,3-triazole were synthesized via a modified microwave-assisted click chemistry technique. Among the synthesized conjugates, 4-((1-(2-chlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)-6-fluoro-2-(trifluoromethyl)quinoline (10g) and 6-fluoro-4-(2-(1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl)ethoxy)-2-(trifluoromethyl)quinoline (12c) show high potency against SARS-CoV-2. The selectivity index (SI) of compounds 10g and 12c also indicates the significant efficacy compared to the reference drugs.

Design, synthesis and pharmacological screening of novel renoprotective methionine-based peptidomimetics: Amelioration of cisplatin-induced nephrotoxicity.

Cisplatin (CP) is an effective chemotherapeutic agent for treatment of various types of cancer, however efforts are needed to reduce its toxic side effect. Previous studies revealed promising effect of peptides in decreasing CP induced nephrotoxicity. Herein, novel Met-based peptidomimetics were synthesized using N-acylbenzotriazole as acylating agent in high yield. Evaluation of renoprotective effect of the synthesized targets on CP treated kidney cell line (LLC-PK1) revealed that pretreatment with 1/3 IC50 of targets II, IIIa-g attenuated CP induced cell death where the IC50 of CP was raised from 3.28 µM to 9.25-41.1 µM. The most potent compounds IIIg, II and IIIb exhibited antioxidative stress in CP-treated LLC-PK1 cells as confirmed by raising GSH/GSSG ratio and SOD concentration as well as decreasing ROS and MDA. Additionally, in vivo experiments using Sprague Dawley rats showed renoprotective effect of IIIg against CP-induced nephrotoxicity as evidenced by improved results of renal function tests and attenuated CP-induced renal structural injury. Moreover, antioxidant activity of IIIg was demonstrated via its ability to reduce renal MDA level and up-regulate renal antioxidant element GSH level. Further, immunohistochemistry of renal specimens showed the ability of IIIg to restore CP-induced suppression of Nrf2. Interestingly, in vivo and in vitro studies demonstrated that IIIg had no effect on CP antiproliferative activity. An assessment of the ADMET properties revealed that targets IIIg, II and IIIb showed good drug-likeness in terms of their physicochemical, pharmacokinetic properties. The findings presented here showcase that IIIg is a promising renoprotective candidate with antioxidative stress potential.

Magnetic ZnO Crystal Nanoparticle Growth on Reduced Graphene Oxide for Enhanced Photocatalytic Performance under Visible Light Irradiation.

Magnetite zinc oxide (MZ) (Fe3O4/ZnO) with different ratios of reduced graphene oxide (rGO) was synthesized using the solid-state method. The structural and optical properties of the nanocomposites were analyzed using transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman spectroscopy, Fourier-transform infrared spectroscopy (FTIR), ultraviolet-visible diffuse reflectance spectroscopy (UV-Vis/DRS), and photoluminescence (PL) spectrophotometry. In particular, the analyses show higher photocatalytic movement for crystalline nanocomposite (MZG) than MZ and ZnO nanoparticles. The photocatalytic degradation of methylene blue (MB) with crystalline ZnO for 1.5 h under visible light was 12%. By contrast, the photocatalytic activity for MZG was more than 98.5%. The superior photocatalytic activity of the crystalline nanocomposite was detected to be due to the synergistic effect between magnetite and zinc oxide in the presence of reduced graphene oxide. Moreover, the fabricated nanocomposite had high electron-hole stability. The crystalline nanocomposite was stable when the material was used several times.

Discovery of novel quinoline-based analogues of combretastatin A-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect.

A new series of quinoline derivatives of combretastatin A-4 have been designed, synthesised and demonstrated as tubulin polymerisation inhibitors. These novel compounds showed significant antiproliferative activities, among them, 12c exhibited the most potent inhibitory activity against different cancer cell lines (MCF-7, HL-60, HCT-116 and HeLa) with IC50 ranging from 0.010 to 0.042 µM, and with selectivity profile against MCF-10A non-cancer cells. Further mechanistic studies suggest that 12c can inhibit tubulin polymerisation and cell migration, leading to G2/M phase arrest. Besides, 12c induces apoptosis via a mitochondrial-dependant apoptosis pathway and caused reactive oxygen stress generation in MCF-7 cells. These results provide guidance for further rational development of potent tubulin polymerisation inhibitors for the treatment of cancer.HighlightsA novel series of quinoline derivatives of combretastatin A-4 have been designed and synthesised.Compound 12c showed significant antiproliferative activities against different cancer cell lines.Compound 12c effectively inhibited tubulin polymerisation and competed with [3H] colchicine in binding to tubulin.Compound 12c arrested the cell cycle at G2/M phase, effectively inducing apoptosis and inhibition of cell migration.

Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity.

A novel series of quinoline derivatives of combretastatin A-4 incorporating rigid hydrazone and a cyclic oxadiazole linkers were synthesized and have demonstrated potent tubulin polymerization inhibitory properties. Many of these novel derivatives have shown significant antiproliferative activities in the submicromolar range. The most potent compound, 19h, demonstrated superior IC50 values ranging from 0.02 to 0.04 µM against four cancer cell lines while maintaining low cytotoxicity in MCF-10A non-cancer cells, thereby suggesting 19h's selectivity towards proliferating cancer cells. In addition to tubulin polymerization inhibition, 19h caused cell cycle arrest in MCF-7 cells at the G2/M phase and induced apoptosis. Collectively, these findings indicate that 19h holds potential for further investigation as a potent chemotherapeutic agent targeting tubulin.

Design and synthesis of novel pyrazolo[3,4-d]pyrimidin-4-one bearing quinoline scaffold as potent dual PDE5 inhibitors and apoptotic inducers for cancer therapy.

PDE5 targeting represents a new and promising strategy for apoptosis induction and inhibition of tumor cell growth due to its over-expression in diverse types of human carcinomas. Accordingly, we report the synthesis of series of pyrazolo[3,4-d]pyrimidin-4-one carrying quinoline moiety (11a-r) with potential dual PDE5 inhibition and apoptotic induction for cancer treatment. These hybrids were structurally elucidated and characterized with variant spectroscopic techniques as 1H NMR, 13C NMR and elemental analysis. The assessment of their anticancer activities has been declared. All the rationalized compounds 11a-r have been selected for their cytotoxic activity screening by NCI against 60 cell lines. Compounds 11a, 11b, 11j and 11k were the most active hybrids. Among all, compound 11j was further selected for five dose tesing and it displayed outstanding activity with strong antitumor activity against the nine tumor subpanels tested with selectivity ratios ranging from 0.019 to 8.3 at the GI50 level. Further, the most active targets 11a, b, j and k were screened for their PDE5 inhibitory activity, compound 11j (with IC50 1.57 nM) exhibited the most potent PDE5 inhibitory activity. Moreover, compound 11j is also showed moderate EGFR inhibition with IC50 of 5.827 ± 0.46 µM, but significantly inhibited the Wnt/ß-catenin pathway with IC501286.96 ± 12.37 ng/mL. In addition, compound 11j induced the intrinsic apoptotic mitochondrial pathway in HepG2 cells as evidenced by the lower expression levels of the anti-apoptotic Bcl-2 protein, and the higher expression of the pro-apoptotic protein Bax, p53, cytochrome c and the up-regulated active caspase-9 and caspase-3 levels. All results confirmed by western blotting assay. Compound 11j exhibit pre G1 apoptosis and cell cycle arrest at G2/M phase. In conclusion, hybridization of quinoline moiety with the privileged pyrazolo[3,4-d]pyrimidinon-4-one structure resulted in highly potent anticancer agent, 11j, which deserves more study, in particular, in vivo and clinical investiagtions, and it is expected that these results would be applied for more drug discovery process.

An Efficient Greener Approach for N-Acylation of Amines in Water Using Benzotriazole Chemistry.

A straightforward, mild and cost-efficient synthesis of various arylamides in water was accomplished using versatile benzotriazole chemistry. Acylation of various amines was achieved in water at room temperature as well as under microwave irradiation. The developed protocol unfolds the synthesis of amino acid aryl amides, drug conjugates and benzimidazoles. The environmentally friendly synthesis, short reaction time, simple workup, high yields, mild conditions and free of racemization are the key advantages of this protocol.

Design, synthesis and anticancer activity of novel valproic acid conjugates with improved histone deacetylase (HDAC) inhibitory activity.

Twenty-five valproic acid conjugates have been designed and synthesized. All target compounds were explored for their in vitro anti-proliferative activities using the MTT-based assay against four human cancer cell lines includingliver (HePG2), colon (HCT116), breast (MCF7) and cervical (HeLa) carcinoma cell lines. Out of six valproic acid-amino acid conjugates 2a-f. Only cysteine containing conjugate 2f showed the significant activity (IC50 9.10 µM against HePG2 and 6.81 µM against HCT116). However conjugate 2j showed broad-spectrum antitumor activity against all cell lines tested. In addition, conjugates 4j and 4k which contains phenyl hydrazide and hydroxamic acid group, respectively, also showed broad spectrum activity. Furthermore, six compounds were screened for HDAC 1-9 isozymes inhibitory activities. Compounds 2j, 4j and 4k manifested a higher inhibitory activity more than valproic acid but less than SAHA. In addition, the in vivo antitumor screening of 2j, 4j and 4k was done and the results have shown that 2j, 4j and 4k, particularly 4j, showed a significant decrease in tumor size and presented a considerable decrease in viable EAC count. Docking study of selectedcompound 4j revealed that it can bind nicely to the binding pocket of HDAC 1, 2, 3, 4 and HDAC 8. The results suggest that compounds 2j, 4j and 4k, particularly 4j, may be promising lead candidates for the development of novel targeted anti-tumor drug potentially via inhibiting HDACs.

Synthesis of imidazolidine-2,4-dione and 2-thioxoimidazolidin-4-one derivatives as inhibitors of virulence factors production in Pseudomonas aeruginosa.

In an attempt to counteract bacterial pathogenicity, a set of novel imidazolidine-2,4-dione and 2-thioxoimidazolidin-4-one derivatives was synthesized and evaluated as inhibitors of bacterial virulence. The new compounds were characterized and screened for their effects on the expression of virulence factors of Pseudomonas aeruginosa, including protease, hemolysin, and pyocyanin. Imidazolidine-2,4-diones 4c, 4j, and 12a showed complete inhibition of the protease enzyme, and they almost completely inhibited the production of hemolysin at 1/4 MIC (1/4 minimum inhibitory concentration; 1, 0.5, and 0.5 mg/ml, respectively). 2-Thioxoimidazolidin-4-one derivative 7a exhibited the best inhibitory activity (96.4%) against pyocyanin production at 1 mg/ml (1/4 MIC). A docking study was preformed to explore the potential binding interactions with quorum-sensing receptors (LasR and RhlR), which are responsible for the expression of virulence genes.

Design, synthesis, antimicrobial, and DNA gyrase inhibitory properties of fluoroquinolone-dichloroacetic acid hybrids.

A series of new fluoroquinolone conjugates 8a-g and 9a-f were synthesized via benzotriazole-mediated synthetic approach with good yield and purity. Some of the synthesized analogs exhibited significant antibacterial properties against Escherichia coli and Staphylococcus aureus with potency higher than that of the parent drugs through in vitro standard bioassay procedure (conjugates 8c and 8d reveal antimicrobial properties with potency 1.9, 61.9, 20.7 and 2.4, 37.1, 8.3 folds relative to the parent antibiotic 6 against E. coli, S. aureus, and Enterococcus faecalis, respectively). The observed experimental data were supported by enzymatic DNA gyrase inhibitory property. Developed BMLR-QSAR model validates the observed experimental data and recognizes the parameters responsible for the enhanced antibacterial properties.

A Chromosome 13 locus is associated with male-specific mortality in mice.

BACKGROUND AND AIM: Mortality is a highly complex trait influenced by a wide array of genetic factors. METHODS: We examined a population of 1200 mice that were F2 generation offspring of a 4-way reciprocal cross between C57BL6/J and DBA2/J strains. Animals were sacrificed at age 200, 500, or 800 days and genotyped at 96 markers. The 800 days old cohort, which were the survivors of a much larger breeding group, were examined for enriched frequency of alleles that benefit survival and depletion of alleles that reduce survival. RESULTS: Loci on Chr 13 in males and on Chr X in females were significantly distorted from Mendelian expectations, even after conservative correction for multiple testing. DBA2/J alleles between 35 and 80 Mb on Chr 13 were underrepresented in the age 800 male animals. D2 genotypes in this region were also associated with premature death during behavioral testing. Furthermore, confirmatory analysis showed BXD recombinant inbred strains carrying the D2 alleles in this region had shorter median survival. Exploration of available pathology data indicated that a syndrome involving dental malocclusions, pancreatic islet hypertrophy, and kidney lipidosis may have mediated the effects of DBA alleles on mortality specifically in male mice. The heterozygote advantage locus on the X Chr was not found to be associated with any pathology. CONCLUSIONS: These results suggest a novel locus influencing survival in the B6/D2 genetic background, perhaps via a metabolic disorder that emerges by 200 days of age in male animals.

Synthesis, molecular docking and anti-inflammatory screening of novel quinoline incorporated pyrazole derivatives using the Pfitzinger reaction II.

In continuation of our study of novel quinolines with anti-inflammatory activity using the Pfitzinger reaction, several new quinoline derivatives were synthesized and tested for their anti-inflammatory and ulcerogenic effect. A docking study on the COX-2 binding pocket was carried out for the target compounds to rationalize the possible selectivity of them against COX-2 enzyme. The most active compounds (5a, 8a and 11a) were found to be superior to celecoxib. Compound 11a demonstrated the highest anti-inflammatory activity as well as the best binding profiles into the COX-2 binding site. Moreover, compounds 9c, 9e, 10a and 11a were devoid of ulcerogenic activity.

Design, synthesis, and molecular modelling of pyridazinone and phthalazinone derivatives as protein kinases inhibitors.

The design and synthesis of pyridazinone and phthalazinone derivatives are described. Newly synthesized compounds were tested on a panel of four kinases in order to evaluate their activity and potential selectivity. In addition, the promising compounds were tested on four cancer cell lines to examine cytotoxic effects. The compounds inhibited DYRK1A and GSK3 with different activity. SAR analysis and docking calculations were carried out to aid in the interpretation of the results. Taken together, our findings suggest that pyridazinone and phthalazinone scaffolds are interesting starting points for design of potent GSK3 and DYRK1A inhibitors.