Bis(dimethylpyrazolyl)-aniline-s-triazine derivatives as efficient corrosion inhibitors for C-steel and computational studies.

4,6-Bis(3,5-dimethyl-1H-pyrazol-1-yl)-N-phenyl-1,3,5-triazin-2-amine (PTA-1), N-(4-bromophenyl)-4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazin-2-amine (PTA-2) and 4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-N-(4-methoxyphenyl)-1,3,5-triazin-2-amine (PTA-3) were synthesized and characterized. Their corrosion inhibition of carbon C-steel in 0.25 M H2SO4 was studied by electrochemical impedance. The inhibition efficiency (IE%) of triazine was superior due to the cumulative inhibition of triazine core structure and pyrazole motif. Potentiodynamic polarizations suggested that s-triazine derivatives behave as mixed type inhibitors. The IE% values were 96.5% and 93.4% at 120 ppm for inhibitor PTA-2 and PTA-3 bearing -Br and -OCH3 groups on aniline, respectively. While PTA-1 without an electron donating group showed only 79.0% inhibition at 175 ppm. The adsorption of triazine derivatives followed Langmuir and Frumkin models. The values of adsorption equilibrium constant K°ads and free energy change ΔG°ads revealed that adsorption of inhibitor onto steel surface was favoured. A corrosion inhibition mechanism was proposed suggesting the presence of physical and chemical interactions. Density functional theory computational investigation corroborated nicely with the experimental results. Monte Carlo simulation revealed that the energy associated with the metal/adsorbate arrangement dE ads/dN i, for both forms of PTA-2 and PTA-3 with electron donating groups (-439.73 and -436.62 kcal mol-1) is higher than that of PTA-1 molecule (-428.73 kcal mol-1). This aligned with experimental inhibition efficiency results.

Green Synthesis of Magnetic Supramolecules ß-Cyclodextrin/Iron Oxide Nanoparticles for Photocatalytic and Antibacterial Applications.

Iron oxide nanoparticles (Fe3O4NPs) are a fascinating field of study due to their wide range of practical applications in environmental and medical contexts. This study presents a straightforward, environmentally friendly method for producing Fe3O4NPs utilizing ß-cyclodextrin (ß-CD) as a reducing and capping agent. This approach results in the rapid and effective eco-friendly synthesis of ß-CD/Fe3O4NPs. The properties and characteristics of ß-CD/Fe3O4NPs were investigated using various methods, including ultraviolet-visible (UV/vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), thermogravimetry analysis (TGA), and vibrating-sample magnetometry (VSM). The absorption of ß-CD/Fe3O4NPs caused a distinct peak at 349 nm, as evidenced by the results of UV/vis studies. This peak was attributed to the absorption of surface plasmon resonance. The crystalline nature of ß-CD/Fe3O4NPs was confirmed through XRD analysis. The SEM and TEM analyses have verified the geometry and structural characteristics of ß-CD/Fe3O4NPs. The ß-CD/Fe3O4NPs exhibited remarkable effectiveness in the decomposing efficiency (%) of methylene blue (MB) dye with 52.2, 94.1, and 100% for 0.2, 0.4, and 0.6 g ß-CD/Fe3O4NPs, respectively. In addition, the highest efficiency in hunting radicals was observed (347.2 ± 8.2 mg/g) at 100 mg/mL ß-CD/Fe3O4NPs; the combination of ß-CD/Fe3O4NPs exhibited remarkable effectiveness in inhibiting the growth of some bacteria that cause infections. The capabilities of ß-CD/Fe3O4NPs for various applications showed that these materials could be used in photocatalytic, antioxidants, and antibacterial. Additionally, the eco-friendly synthesis of these materials makes them a promising option for the remediation of harmful pollutants and microbes.

Pyrazolyl-s-triazine with indole motif as a novel of epidermal growth factor receptor/cyclin-dependent kinase 2 dual inhibitors.

A series of pyrazolyl-s-triazine compounds with an indole motif was designed, synthesized, and evaluated for anticancer activity targeting dual EGFR and CDK-2 inhibitors. The compounds were tested for cytotoxicity using the MTT assay. Compounds 3h, 3i, and 3j showed promising cytotoxic activity against two cancer cell lines, namely A549, MCF-7, and HDFs (non-cancerous human dermal fibroblasts). Compound 3j was the most active candidate against A549, with an IC50 of 2.32 ± 0.21 µM. Compounds 3h and 3i were found to be the most active hybrids against MCF-7 and HDFs, with an IC50 of 2.66 ± 0.26 µM and 3.78 ± 0.55 µM, respectively. Interestingly, 3i showed potent EGFR inhibition, with an IC50 of 34.1 nM compared to Erlotinib (IC50 = 67.3 nM). At 10 µM, this candidate caused 93.6% and 91.4% of EGFR and CDK-2 inhibition, respectively. Furthermore, 3i enhanced total lung cancer cell apoptosis 71.6-fold (43.7% compared to 0.61% for the control). Given the potent cytotoxicity exerted by 3i through apoptosis-mediated activity, this compound emerges as a promising target-oriented anticancer agent.

Synthesis and characterization of photo-crosslinkable cinnamate-functionalized pectin.

The polysaccharide pectin (PC) was functionalized with the photo-responsive cinnamic acid hydrazide (CN) to produce the photo-crosslinkable PC-CN hydrogel material that was then evaluated as a carrier for encapsulation of the drug model aspirin. Cinnamic acid hydrazide was first prepared and then incorporated with the abundant -COOCH3 groups on the pectin chain via hydrazide linkage. The obtained polymeric derivatives have been characterized by means of instrumental techniques including FTIR and NMR. The obtained PC-CN hydrogels with different cinnamic functionality were also freeze-dried and examined by SEM, which indicated more coherent hydrogel texture by increasing the cinnamic functionalization. The effect of the photo-curing time, as well as the functionalization degree, on the swelling and gelation of the obtained hydrogel was also studied to evaluate the potential of the developed material in drug delivery systems using aspirin as a common and available drug model. The developed PC-CN hydrogel materials exhibited high potential as a drug carrier that enables the control of the drug release via optimizing both the degree of cinnamic functionality and the photo-curing time.

Corrigendum: Pyrazolyl-s-triazine with indole motif as a novel of epidermal growth factor receptor/cyclin-dependent kinase 2 dual inhibitors.

[This corrects the article DOI: 10.3389/fchem.2022.1078163.].

Syntheses and Structural Investigations of Penta-Coordinated Co(II) Complexes with Bis-Pyrazolo-S-Triazine Pincer Ligands, and Evaluation of Their Antimicrobial and Antioxidant Activities.

Two penta-coordinated [Co(MorphBPT)Cl2]; 1 and [Co(PipBPT)Cl2]; 2 complexes with the bis-pyrazolyl-s-triazine pincer ligands MorphBPT and PipBPT were synthesized and characterized. Both MorphBPT and PipBPT act as NNN-tridentate pincer chelates coordinating the Co(II) center with one short Co-N(s-triazine) and two longer Co-N(pyrazole) bonds. The coordination number of Co(II) is five in both complexes, and the geometry around Co(II) ion is a distorted square pyramidal in 1, while 2 shows more distortion. In both complexes, the packing is dominated by Cl…H, C-H…π, and Cl…C (anion-π stacking) interactions in addition to O…H interactions, which are found only in 1. The UV-Vis spectral band at 564 nm was assigned to metal-ligand charge transfer transitions based on TD-DFT calculations. Complexes 1 and 2 showed higher antimicrobial activity compared to the respective free ligand MorphBPT and PipBPT, which were not active. MIC values indicated that 2 had better activity against S. aureus, B. subtilis, and P. vulgaris than 1. DPPH free radical scavenging assay revealed that all the studied compounds showed weak to moderate antioxidant activity where the nature of the substituent at the s-triazine core has a significant impact on the antioxidant activity.

Fe(III) Complexes Based on Mono- and Bis-pyrazolyl-s-triazine Ligands: Synthesis, Molecular Structure, Hirshfeld, and Antimicrobial Evaluations.

The self-assembly of iron(III) chloride with three pyrazolyl-s-triazine ligands, namely 2,4-bis(3,5-dimethyl-1H-pyrazol-1-yl)-6-(piperidin-1-yl)-1,3,5-triazine (PipBPT), 4-(4,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazin-2-yl)morpholine (MorphBPT), and 4,4'-(6-(3,5-dimethyl-1H-pyrazol-1-yl)-1,3,5-triazine-2,4-diyl)dimorpholine (bisMorphPT) afforded [Fe(PipBPT)Cl2][FeCl4] (1), [Fe(MorphBPT)Cl2][FeCl4] (2), and [H(bisMorphPT)][FeCl4]. bisMorphPT.2H2O (3), respectively, in good yield. In complexes 1 and 2, the Fe(III) is pentacoordinated with three Fe-N interactions from the pincer ligand and two coordinated chloride anions in the inner sphere, and FeCl4¯ in the outer sphere. Complex 3 is comprised of one protonated ligand as cationic part, one FeCl4¯ anion, and one neutral bisMorphPT molecule in addition to two crystallized water molecules. Analysis of molecular packing using Hirshfeld calculations indicated that H…H and Cl…H are the most important in the molecular packing. They comprised 40.1% and 37.4%, respectively in 1 and 32.4% and 37.8%, respectively in 2. Complex 1 exhibited the most bioactivity against the tested microbes while 3 had the lowest bioactivity. The bisMorphPT and MorphBPT were inactive towards the tested microbes while PipBPT was active. As a whole, the Fe(III) complexes have enhanced antibacterial and antifungal activities as compared to the free ligands.

Ultrasonically Assisted N-Cyanoacylation and Synthesis of Alkyl(4-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)benzoyl)amino Acid Ester Derivatives.

This work represents the use of N-3-(3,5-dimethyl-1H-pyrazol-1-yl)-3-oxopropanenitrile as a cyanoacetylating agent for the synthesis of cyanoacetamide benzoic acid and benzophenone derivatives by two different methods, namely, conventional heating and ultrasonication. The cyanoacetamide derivatives were subjected to cyclization to produce N-substituted 2-pyridone derivatives under conventional heating and by an ultrasonic method as well. The ultrasonic method afforded the products in less reaction time with high yields and purities compared to the conventional method, as observed from their spectral data. N-(4-Carboxy phenyl)-4,6-dimethyl-3-cyano-2-pyridone was coupled with different amino acid esters by the OxymaPure/DIC methodology under traditional and ultrasonic conditions. Again, ultrasonication assisted the coupling step and afforded the products with higher yields and purities compared to the traditional method. Fourier transform infrared spectroscopy, NMR (1H and 13C), elemental analysis, and LC-MS were used to determine the structures of all compounds. Finally, a feature of this protocol is exploring the utilization of ultrasonication as an eco-friendly alternative conventional heating method for N-cyanoacylation and synthesis of N-substituted pyridinone derivatives and as a coupling method for the formation of an amide bond, which might be of interest for many researchers.

Synthesis, Anti-proliferative Activity, and Molecular Docking Study of New Series of 1,3-5-Triazine Schiff Base Derivatives.

Based on the use of s-triazine as a scaffold, we report here a new series of s-triazine Schiff base derivatives and their anti-proliferative activity against two cancer cell lines: human breast carcinoma (MCF-7), and colon cancer (HCT-116) compared with tamoxifen as a reference compound. Several derivatives exhibited growth inhibition activity in the sub-micromolar range. The results reveal that the s-triazine Schiff base derivatives showed varied activities and that the substituents on the s-triazine core have a great effect on the anti-proliferative activity. Compounds with a piperidino and benzylamino substituent on the s-triazine moiety 4b and 4c were most effective in both cell lines compared to the reference compound used. In addition, compound 4b has a para chlorine atom on the benzylidine residue, demonstrating the most potent activity with IC50 values of 3.29 and 3.64 µM in MCF-7 and HCT-116, respectively. These results indicate that in general, the nature of the substituents on the triazine core and the type of substituent on the benzilyldene ring significantly influenced the anti-proliferative activity. The results obtained from the anti-proliferative activity and the molecular docking study indicate that s-triazine-hydrazone derivatives may be an excellent scaffold for the development of new anti-cancer agents.

Synthesis and Characterization of New Series of 1,3-5-Triazine Hydrazone Derivatives with Promising Antiproliferative Activity.

A new series of s-triazine hydrazone derivatives was prepared based on the reaction of 6-hydrazino-2,4-disubstituted-s-triazine with p-substituted benzaldehyde derivatives using a straightforward synthetic pathway. The antiproliferative activity of all synthesized compounds was evaluated against two human cancer cell lines; breast cancer MCF-7 and colon carcinoma HCT-116 using MTT assay. Among all, 11 compounds have shown strong to moderate antiproliferative activity with IC50 values in the range 1.01-18.20 µM in MCF-7 and 0.97-19.51 µM in HCT-116. The best results were obtained with 4,4'-(6-(2-(pyridin-2-ylmethylene)hydrazinyl)-1,3,5-triazine-2,4-diyl) dimorpholine 11 (IC50 = 1.0 µM and 0.98 µM in MCF-7 and HCT-116 cell lines, respectively). The substituents on the s-triazine core as well as the substituent at the benzylidene moiety have a great effect on the antiproliferative activity. Whereas compounds containing dimorpholino-s-triazine derivatives 8a-e showed more potent antiproliferative in MCF-7 compared to their analogs 7a-f (compounds containing two-piperidine rings), compounds containing one piperidine and one morpholine ring 9a-f showed better IC50 values in the range 10.4-22.2 µM. On the other hand, compounds containing two-piperidine rings 7a-f showed more potent antiproliferative in HCT-116 (IC50 values in the range 8.8-19.5 µM) than their analogs 8a-e and 9a-f.

Simple Approaches for the Synthesis of AgNPs in Solution and Solid Phase Using Modified Methoxypolyethylene Glycol and Evaluation of Their Antimicrobial Activity.

PURPOSE: Simple methodology for preparation of metal nanoparticles such as AgNPs uses an methanolic aqueous medium at room temperature or a solvent-free procedure under microwave irradiation. The prepared AgNPs showed a significant antimicrobial effect against Gram-positive bacteria, Gram-negative bacteria, and fungi. METHODS: The modified methoxypolyethylene glycol bishydrazino-s-triazine (mPEGTH2) showed remarkable activity for reducing Ag+ to Ag0 in an aqueous methanolic solution and using a solvent-free method (solid phase) under microwave irradiation. In the solid phase synthesis, the size and shape of the AgNPs can be controlled by varying the weight ratio of mPEGTH2 to AgNO3 used. In addition, the antimicrobial activity depends on the ratio of mPEGTH2 to AgNO3. The mPEGTH2-AgNPs (2:1) demonstrated higher antimicrobial activity compared to mPEGTH2-AgNPs (1:1) against Gram-positive bacteria, Gram-negative bacteria, and C.albicans. RESULTS: This work presents simple methods for the synthesis of AgNPs using modified methoxypolyethylene glycol with bishydrazino-s-triazine (mPEGTH2); a solution method, using methanol-water medium at room temperature, and a solvent-free (solid phase) method, employing microwave irradiation or direct heating which could be used for the preparation of AgNPs on large scale. In the solid phase, ratios of mPEGTH2 to AgNO3 (1:1 or 2:1, respectively) are very important to control the size and shape of AgNPs. While in solution phase is not necessary where the molar ratio used is 10:1. Most of the experimental methods resulted in AgNPs ranging in size from 7 to 10 nm as observed from XRD and TEM characterization. The antimicrobial activity of the AgNPs was also dependent on the weight ratio of mPEGTH2 to AgNO3, with a large effect as observed when using the solvent-free method. The mPEGTH2-AgNPs (2:1) demonstrated higher antimicrobial activities compared to mPEGTH2-AgNPs (1:1) against S. aureus, S. epidermidis, E. faecalis, E. coli, P. aeruginosa, S. typhimurium, and C. albicans. In all cases, the MICs and MBCs of mPEGTH2-AgNPs (1:1) were lower than those of mPEGTH2-AgNPs (2:1). CONCLUSION: In summary, mPEGTH2-AgNPs (2:1) is a promising candidate to kill pathogenic microbes. In particular, the method used for the preparation of AgNPs by using polyethylene glycol polymer modified with bishydrazino-s-triazine has the most potential and would be the most cost-effective method. This method of the synthesis of nanoparticles may be suitable for the preparation of other metal nanoparticles, which would allow for numerous applications in medicinal and industrial.

Synthesis and characterisation of thiobarbituric acid enamine derivatives, and evaluation of their α-glucosidase inhibitory and anti-glycation activity.

A new series of thiobarbituric (thiopyrimidine trione) enamine derivatives and its analogues barbituric acid derivatives was synthesised, characterised, and screen for in vitro evaluation of α-glucosidase enzyme inhibition and anti-glycation activity. This series of compounds were found to inhibit α-glucosidase activity in a reversible mixed-type manner with IC50 between 264.07 ± 1.87 and 448.63 ± 2.46 µM. Molecular docking studies indicated that compounds of 3g, 3i, 3j, and 5 are located close to the active site of α-glucosidase, which may cover the active pocket, thereby inhibiting the binding of the substrate to the enzyme. Thiopyrimidine trione derivatives also inhibited the generation of advanced glycation end-products (AGEs), which cause long-term complications in diabetes. While, compounds 3a-k, 5, and 6 showed significant to moderate anti-glycation activity (IC50 = 31.5 ± 0.81 to 554.76 ± 9.1 µM).