Yousery E. Sherif

Synthesis, spectral, optical and anti-inflammatory activity of complexes derived from 2-aminobenzohydrazide with some rare earths

Abstract Three new metal complexes derived from Er(III), Dy(III) and Zr(IV) with 2-aminobenzohydrazide (ABH) were synthesized and characterized by elemental analyses, IR, 1H-NMR, ES-MS and transmission electron microscopy (TEM). The morphology and the particle size were determined by TEM. The results showed that the ligand acted as neutral bi-dentate coordinating to the metal ions through the carbonyl oxygen and amidic amino nitrogen. The aromatic amine group remained inert towards coordination. The optical band gap was measured and found to be 3.3, 3.5 and 4.3 eV for Er(III), Dy(III) and Zr(IV), respectively. The optical band gap values indicated a semi-conducting nature of the investigated complexes. The anti-inflammatory and analgesic activities of the tested compounds were determined and compared with standard meloxicam.

Synthesis, characterization, analgesic and anti-inflammation activity of new phthalazines and their Cu(II) and Zn(II) complexes

Abstract1,4-Dioxo-3, 4, 4e, 5, 10, 10a-hexahydro-1H-5,10-benzenobenzo [g] phthalazin-2-yl-thioamide [6a]; 1,4-dioxo-3, 4, 4e, 5, 10, 10a-hexahydro-1H-5, 10-benzenobenzo [g] phthalazin-2-yl-N-pyridylthioamide [6b] and 1,4-dioxo-3, 4, 4e, 5, 10, 10a-hexahydro-1H-5, 10-benzenobenzo[g]phthalazin-2-yl-N-ethylthioamide [6c] and their [Cu(6a-H)(OAc)], [Zn(6a-H)(OAc)], [Cu(6b-H)(H2O)2(OAc)]·3H2O and [Zn(6b-H)(OAc)], [Cu2(6c-H)](OAc)3]·2H2O and [Zn(6c-H)(OAc)] complexes have been synthesized via a reaction between phthalazinedione 6a–c derivatives and the acetate salt of Cu(II) or Zn(II). These compounds were characterized by elemental analysis, spectra (UV–Vis, IR, 1H NMR, 13C NMR, ESR), conductance, thermal analysis and magnetic moments.

Rational design, synthesis, pharmacophore modeling, and docking studies for identification of novel potent DNA-PK inhibitors

Drugs of cancer based upon ionizing radiation or chemotherapeutic treatment may affect breaking of DNA double strand in cell. DNA-PK enzyme has emerged as an attractive target for drug discovery efforts toward DNA repair pathways. Hence, the search for potent and selective DNA-PK inhibitors has particularly considered state-of-the art and several series of inhibitors have been designed. In this article, a novel benchmark DNA-PK database of 43 compounds was built and described. Ligand-based approaches including pharmacophore and QSAR modeling were applied and novel models were introduced and analyzed for predicting activity test for DNA-PK drug candidates. Based upon the modeling results, we gave a report of synthesis of fifteen novel 2-((8-methyl-2-morpholino-4-oxo-4H-benzo[e][1,3]oxazin-7-yl)oxy)acetamide derivatives and in vitro evaluation for DNA-PK inhibitory and antiproliferative activities. These fifteen compounds overall are satisfied with Lipinskis rule of five. The biological testing of target compounds showed five promising active compounds 7c, 7d, 7f, 9e and 9f with micromolar DNA-PK activity range from 0.25 to 5µM. In addition, SAR of the compounds activity was investigated and confirmed that the terminal aryl moiety was found to be quite crucial for DNA-PK activity. Moreover flexible docking simulation was done for the potent compounds into the putative binding site of the 3D homology model of DNA-PK enzyme and the probable interaction model between DNA-PK and the ligands was investigated and interpreted.

Anti-inflammatory activity of (2E,15E)-2-[1-(2-aminophenyl)ethylidineamino]-N′-[1-(2-aminophenyl)ethylidene]benzoic acid hydrazide (AEBH) and some of its nanoparticles rare earth complexes

Complexes of Er(III), Gd(III), and La(III) with (2E,15E)-2-[1-(2-aminophenyl)ethylidineamino]-N′-[1-(2-aminophenyl)ethylidene]benzoic acid hydrazide (AEBH) have been synthesized. The isolated complexes were characterized by elemental analyses, thermal analyses (TGA, DTA), IR, 1H NMR, 13C NMR, ES-MS, TEM, and conductance measurements. The results indicated that the ligand coordinates to La(III), Gd(III), and Er(III) in the keto form as neutral pentadentate ligand. The particle size and morphology have been determined by TEM. In vivo pharmacological evaluation of the synthesized compounds in collagen II—Freund’s adjuvant model proved the presence of anti-inflammatory and analgesic activities of these compounds. Gd(III) complex showed higher effect in comparison with the well-known drug meloxicam.Graphical Abstract

Synthesis, characterization, and anti-rheumatic potential of phthalazine-1,4-dione and its Cu(II) and Zn(II) complexes

Abstract Two new metal complexes derived from the reaction of 2-[(2-hydroxybenzoyl) 2,3,4a,5,10,10a-hexahydro-5,10[1′,2′]-benzenobenzo[g]phthalazine-1,4-dione] (HBPD) with Cu(II) and Zn(II) have been synthesized and characterized by using elemental analysis, spectral analysis (UV–Vis, IR, 1H NMR, 13C NMR), conductance, thermal analysis, and magnetic moments. The in vivo collagen-adjuvant arthritis model in rats revealed a significant antioxidant, analgesic, and anti-rheumatic effects for HBPD and its copper and zinc complexes in comparison with standard piroxicam. The results showed that, the investigated Cu and Zn complexes have higher anti-inflammatory activity than the free ligand.

Design, Synthesis, Characterization, QSAR, Anti-inflammatory and Analgesic Evaluation of Some New Phthalazinediones

BACKGROUND phthalazine derivatives were reported to possess anticonvulsant , cardiotonic , antibacterial, analgesic , anti-inflammatory, and anti-microbial activity. In the current study, we applied the QSAR for prediction of newly phthalazinediones incorporating thioamide moiety aiming to reach a more potent anti-inflammatory and Analgesic agent. METHODS Phthalazinediones 10-15 have been synthesized through condensation of dibenzobarallene 3 with thiosemicarbazides 4-8. One equation was predicted using quantitative structure activity relationship (QSAR) and regression analysis for the anti-inflammatory activity with a regression correlation (R) close to unity. The docking studies were performed to investigate the biological trends of the organic compounds (thiol form) against cyclooxygenas- 2 enzyme, which is a responsible inflammation mediator by using Molgro Virtual Docker (MVD) software. The anti-inflammatory activity and analgesic effect of the thioamides 10-15 were determined by collagen II-adjuvant induced paw edema test in rats. RESULTS Compounds 10, 11, 12, and 14, exhibited promising anti-inflammatory activity. Furthermore, in the pain scoring, compounds 10, 11 and 12 were found to be more effective than piroxicam and the order of the analgesic effect of the investigated compounds is as followed 14 >12 > 10 > 11 > 15. CONCLUSION It is clear from the foregoing that the compound 14 is a promising compound if future pharmacological detailed studies. This is consistent with what has been predictable equation 1 in this study.