Mono- and bis-pyrazolophthalazines: Design, synthesis, cytotoxic activity, DNA/HSA binding and molecular docking studies.

In an attempt to find new potent cytotoxic compounds, several mono- and bis-pyrazolophthalazines 4a-m and 6a-h were synthesized through an efficient, one-pot, three- and pseudo five-component synthetic approach. All derivatives were evaluated for their in vitro cytotoxic activities against four human cancer cell lines of A549, HepG2, MCF-7, and HT29. Compound 4e showed low toxicity against normal cell lines (MRC-5 and MCF 10A, IC50 > 200 µM) and excellent cytotoxic activity against A549 cell line with IC50 value of 1.25 ± 0.19 µM, which was 1.8 times more potent than doxorubicin (IC50 = 2.31 ± 0.13 µM). In addition, compound 6c exhibited remarkable cytotoxic activity against A549 and MCF-7 cell lines (IC50 = 1.35 ± 0.12 and 0.49 ± 0.01 µM, respectively), more than two-fold higher than that of doxorubicin. The binding properties of the best active mono- and bis-pyrazolophthalazine (4e and 6c) with HSA and DNA were fully evaluated by various techniques including UV-Vis absorption, circular dichroism (CD), Zeta potential and dynamic light scattering analyses indicating interaction of the compounds with the secondary structure of HSA and significant change of DNA conformation, presumably via a groove binding mechanism. Additionally, molecular docking and site-selective binding studies confirmed the fundamental interaction of compounds 4e and 6c with base pairs of DNA. Compounds 4e and 6c showed promising features to be considered as potential lead structures for further studies in cancer therapy.

A novel four- and pseudo-five-component reaction: unexpected efficient one-pot synthesis of 4H-thiopyran derivatives.

A facile and convenient novel method is reported for the synthesis of substituted 4H-thiopyrans by reacting aldehydes, malononitrile, carbon disulfide, and primary amines at room temperature in the presence of triethylamine as a catalyst. This reaction affords the desired products in high purity and has advantages of excellent yields, simple work-up procedure, and short reaction time.

Efficient synthesis of benzoacridines and indenoquinolines catalyzed by acidic magnetic dendrimer.

A novel solid acid catalyst with recoverability, named as Fe3O4@SiO2@TAD-G2-SO3H, was successfully synthesized by immobilizing sulfonic acid groups on triazine dendrimer-modified magnetic nanoparticles. This nanomaterial structure and composition were thoroughly characterized using various analytical techniques, including thermogravimetric analysis (TGA), elemental analysis, Fourier transform infrared spectroscopy (FT-IR), energy-dispersive X-ray spectroscopy (EDX), elemental mapping, acid-base titration, X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and vibrating sample magnetometry (VSM). The acid-decorated magnetic dendrimer was served as a highly effective catalyst for the synthesis of tetrahydrobenzo[c]acridin-8(9H)-one and benzo[h]indeno[1,2-b]quinoline-8-one derivatives. The reaction proceeded smoothly under mild conditions through the one-pot condensation of aromatic aldehydes, 1-naphthylamine, and either dimedone or 1,3-indanedione, affording the desired products in high yields ranging from 90 to 96%. The catalyst was easily separated from the reaction mixture by employing a magnetic field, allowing for its recycling up to five times with slight loss in its activity (only 10%). Nearly, quantitative recovery of catalyst (up to 95%) could be obtained from each run. So, this catalyst facilitates the reaction progress and simplifies the purification process. Other remarkable features of this method are operational simplicity, excellent yields, mild condition, and a wide range of substrate applicability.

An immobilized Schiff base-Mn complex as a hybrid magnetic nanocatalyst for green synthesis of biologically active [4,3-d]pyrido[1,2-a]pyrimidin-6-ones.

The immobilization of metal ions on inorganic supports has garnered significant attention due to its wide range of applications. These immobilized metal ions serve as catalysts for chemical reactions and as probes for studying biological processes. In this study, we successfully prepared Fe3O4@SiO2@Mn-complex by immobilizing manganese onto the surface of magnetic Fe3O4@SiO2 nanoparticles through a layer-by-layer assembly technique. The structure of these hybrid nanoparticles was characterized by various analytical techniques, including Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM), and inductively coupled plasma-optical emission spectrometry (ICP-OES). Fe3O4@SiO2@Mn-complex was successfully utilized in the synthesis of biologically active 7-aryl[4,3-d]pyrido[1,2-a]pyrimidin-6(7H)-one derivatives in an aqueous medium, providing environmentally friendly conditions. The desired products were manufactured in high yields (81-95%) without the formation of side products. The heterogeneity of the solid nanocatalyst was assessed using a hot filtration test that confirmed minimal manganese leaching during the reaction. This procedure offers numerous advantages, including short reaction times, the use of a green solvent, the ability to reuse the catalyst without a significant decrease in catalytic activity, and easy separation of the catalyst using an external magnet. Furthermore, this approach aligns with environmental compatibility and sustainability standards.

Deep oxidative desulfurization of simulated and real gas oils by NiFe2O4@SiO2-DETA@POM as a retrievable hybrid nanocatalyst.

Magnetic nanoparticles surrounded with a silica shell are useful materials to immobilize active agents on their surface. Here, a heteropolyacid-functionalized hybrid nanomaterial (NiFe2O4@SiO2-DETA@POM) was prepared and characterized by X-ray powder diffraction patterns (XRD), Fourier-transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA/DTG), vibrating sample magnetometer (VSM), the field emission scanning electron microscopy (FE-SEM), and the electron-dispersive X-ray spectroscopy (EDS). The synthesized hybrid nanostructure was used as a solid nanocatalyst in oxidative desulfurization (ODS) of real fuel and simulated gasoline samples. The ODS process of benzothiophene (BT) and dibenzothiophene (DBT) as model compounds in the presence of NiFe2O4@SiO2-DETA@POM and by using urea-hydrogen peroxide/acetic acid as a safer oxidizing agent was investigated. A good result was obtained by removing 97% of benzothiophene and 98% of dibenzothiophene. Also, 96% of the sulfur compounds were eliminated when the ODS process was tested on a real crude oil sample (600 ppm) under an optimized dosage of nanocatalyst, urea-hydrogen peroxide/acetic acid (0.1 g, 1 g/4 ml) at 50 ºC for 60 min. NiFe2O4@SiO2-DETA@POM could be recycled for five consecutive oxidation runs without significant deterioration in its catalytic activity. The UHP's safety and efficiency as an oxidant, high removal efficacy, short transformation times, easy workup procedure, catalyst reusability, simple separation of nanocatalyst, green conditions, and environmental compatibility and sustainability. The obtained results prove that NiFe2O4@SiO2-DETA@POM is a suitable and efficient hybrid catalyst for the oxidative desulfurization of simulated and real fuels.

Magnetic triazine-based dendrimer as a versatile nanocarrier for efficient antiviral drugs delivery.

Nanoscale engineering is an efficient method for the treatment of multiple infectious diseases. Due to the controllable functionalities, surface properties, and internal cavities, dendrimer-based nanoparticles represent high performance in drug delivery, making their application attractive in pharmaceutical and medicinal chemistry. In this study, a dendritic nanostructure (Fe3O4@SiO2@TAD-G3) was designed and fabricated by grafting a triazine-based dendrimer on a magnetic nanomaterial. The structure of synthesized hybrid nanostructure was characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), energy-dispersive X-ray (EDX) spectroscopy, elemental mapping, scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and vibrating sample magnetometry (VSM). The prepared nanostructure (Fe3O4@SiO2@TAD-G3) combines the unique properties of magnetic nanoparticles and a hyperbranched dendrimer for biomedical applications. Its dual nature and highly exposed active sites, could make the transportation of drugs to targeted sites of interest through the magnetic field. A study was conducted on model drugs loading (Favipiravir and Zidovudine) and in vitro release behaviour of Fe3O4@SiO2@TAD-G3, which was monitored by ultraviolet spectroscopy. The dendritic nanostructure exhibited high drug-loading capacity for Favipiravir (63.2%) and Zidovudine (76.5%). About (90.8% and 80.2%) and (95.5% and 83.4%) of loaded Favipiravir and Zidovudine were released from Fe3O4@SiO2@TAD-G3 at pH 1.5 and 6.8 respectively, within 600 min and at 37 °C. The initial fast release attributed to the drug molecules on the surface of nanostructure while the drugs incorporated deeply into the pores of the Fe3O4@SiO2@TAD-G3 released with a delay. We proposed that Fe3O4@SiO2@TAD-G3 could be tested as an effective carrier in the targeted (cellular or tissue) delivery of drugs. We think that the prepared nanostructure will not deposit in the liver and lungs due to the small size of the nanoparticles.