A versatile, efficient, clean, and facile method was used for the synthesis of pyrano[2,3‐d]pyrimidine derivatives by the one‐pot three‐component condensation reaction of thiobarbituric acid and malononitrile with p‐chlorobenzaldehyde, using Fe3O4 or ZnO or Mn3O4 as nanostructure catalysts. The catalyst could be easily recovered using an external magnet and reused for six cycles with almost a consistent activity. A series of polyheterocyclic compounds containing five and/or six rings fused with each other was designed. The anti‐inflammatory activities for some of the newly synthesized compounds were evaluated. All the synthesized compounds were characterized on the basis of their elemental analyses and spectral data.

Novel candidates of 3-(4-(thiophen-2-yl)-pyridin/pyran/pyrimidin/pyrazol-2-yl)-1H-indole derivatives (2–12) were designed by pairing the pyridine/pyrane/pyrimidine/pyrazole heterocycles with indole and thiophene to investigate their potential activities as (2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) inhibitors. The purpose of these derivatives’ modification is to create high-efficiency antioxidants, especially against ABTS, as a result of the efficiency of this set of key heterocycles in the inhibition of ROS. Herein, 2D QSAR modeling was performed to recommend the most promising members for further in vitro investigations. Furthermore, the pharmacological assay for antioxidant activity evaluation of the yielded indole-based heterocycles was tested against ABTS (2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid); by utilizing ascorbic acid as the standard. Candidate 10 showed higher antioxidant activity (IC50 = 28.23 μg/mL) than ascorbic acid itself which achieved (IC50 = 30.03 μg/mL). Moreover, molecular docking studies were performed for the newly designed and synthesized drug candidates to propose their mechanism of action as promising cytochrome c peroxidase inhibitors compared to ascorbic acid as a reference standard. Our findings could be promising in the medicinal chemistry scope for further optimization of the newly designed and synthesized compounds regarding the introduced structure-activity relationship study (SAR) in order to get a superior antioxidant lead compound in the near future.

A novel semicarbazone NO 2 ligand, H 2 L, was synthesized. The ligand reacted with several metal ions such as Cu(II), Ni(II), Co(II), Fe(III), Cr(III), and Mn(II) in a molar ratio 1:1 (M:L). The H 2 L ligand and its metal complexes were characterized by electronic, infrared, mass, nuclear magnetic resonance, electron spin resonance spectra, as well as elemental analysis, thermal analysis, molar conductance, and magnetic susceptibility measurements. The Coats-Redfern equations were used to calculate the kinetic parameters (E a , A, ΔH, ΔS, and ΔG) of the thermal decomposition stages. The H 2 L ligand acts as dianionic NO 2 tridentate in all complexes and coordinates through enolate oxygen, azomethine nitrogen, and deprotonated OH group. The geometrical arrangements in all metal complexes were octahedral geometries. Based on density functional theory (DFT) level implemented in the Gaussian 09 program at B3LYP/6-311G(d,p) level, the molecular structural parameters of the ligand and its metal complexes were calculated, and the theoretical data were connected with the experimental results. The antimicrobial activity of the current compounds was examined against Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram-negative bacteria (Salmonella typhimurium and Escherichia coli), yeast (Candida albicans), and fungus (Aspergillus fumigatus). The antitumor activity of the ligand and its metal complexes was investigated against HepG2 cell line, which revealed promising IC 50 values comparable with that of Cis-platin. All synthesized compounds were also subjected to molecular docking studies to investigate their binding pattern and affinity for the VEGFR-2 active site and correlated with antitumor data.

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