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.

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.