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A quinoxaline‐based ligand, 6,7‐dimethyl‐2,3‐di(2‐pyridyl)quinoxaline (Me2dpq), and its unique binuclear Co(II)‐Me2dpq complex were prepared and analyzed using single crystal X‐ray diffraction and several spectroscopy techniques. Hirshfeld surface analyses were also used to clarify the Me2dpq ligand and the Co(II)‐Me2dpq crystal packing. The Co(II)‐Me2dpq complex crystallized in triclinic P‐1 space group and exhibited a distorted trigonal bipyramidal geometry around the cobalt(II) ion. Each Co(II) ion coordinated to a Me2dpq ligand through two N donor centers from pyridyl and quinoxaline rings along with a terminal Cl and two bridged Cl atoms. The binding properties of the ligand and its complex with CT‐DNA were studied by several techniques, namely UV–Vis spectroscopy, fluorescence quenching, viscosity measurements, thermal denaturation, and gel electrophoresis. The CT‐DNA binding interaction tests demonstrated that both the Co(II)‐Me2dpq complex and its parent ligand bind to DNA in an intercalative way. The antioxidant studies of the novel Co(II)‐Me2dpq complex illustrated significant activity against DPPH• and OH•· radicals. The in vitro cytotoxic effect of Me2dpq ligand and its Co(II)‐complex on MCF‐7 and Hep‐G2 tumor cell lines was evaluated by using the MTT assay. The studies showed that the Co(II)‐Me2dpq complex had superior activity toward the tested cell lines. Molecular docking studies of synthesized compounds were employed to figure out the way they would associate with a biologically macromolecular target B‐DNA (PDB: 1BNA). Thus, this study is anticipated to provide novel opportunities for the successful utilization of the synthesized compounds in many medical domains. [ABSTRACT FROM AUTHOR]

A novel Schiff base ligand (HL), derived from the condensation of phenylethanolamine and quinoline‐2‐carboxaldehyde, and its coordination complexes with some transition metal ions, Mn(II), Co(II), Ni(II), Cu(II), Zn(II), and Pd(II), were synthesized. The reported new compounds were characterized using different analytical and spectroscopic techniques. The structure of HL and its cobalt complex was also solved by conventional X‐ray diffraction technique. Hirshfeld surface analysis of the ligand and cobalt complexes was investigated. Interesting structural features with unique hydrogen bonding formation were observed. Molecular geometries of HL and the reported complexes were investigated using the DFT‐B3LYP level of theory. The quantum global reactivity descriptors were also calculated. Biological screening and molecular docking studies of the ligand and complexes are reported to explore their potential application as therapeutic drugs. The biological studies and molecular docking were correlated to each other and with the quantum reactivity descriptors. The studies supported that the complexes could bind to DNA via intercalative mode and showed various DNA binding potency. [ABSTRACT FROM AUTHOR]

[Display omitted] • Dinucleoside polyphosphates (NpxNs) were studied as human adenylate kinase isoenzyme 1 (hAK1) inhibitors. • Docking studies on hAK1-NpxN interactions mainly agree with the experimental results. • For three dinucleoside polyphosphates, an IC 50 value of less than 1 µM was reported. • Two PLS-regression-based QSAR models were built for human AK1. Adenylate kinase (AK) plays a crucial role in the metabolic monitoring of cellular adenine nucleotide homeostasis by catalyzing the reversible transfer of a phosphate group between ATP and AMP, yielding two ADP molecules. By regulating the nucleotide levels and energy metabolism, the enzyme is considered a disease modifier and potential therapeutic target for various human diseases, including malignancies and inflammatory and neurodegenerative disorders. However, lacking approved drugs targeting AK hinders broad studies on this enzyme's pathological importance and therapeutic potential. In this work, we determined the effect of a series of dinucleoside polyphosphate derivatives, commercially available (11 compounds) and newly synthesized (8 compounds), on the catalytic activity of human adenylate kinase isoenzyme 1 (hAK1). The tested compounds belonged to the following groups: (1) diadenosine polyphosphates with different phosphate chain lengths, (2) base-modified derivatives, and (3) phosphate-modified derivatives. We found that all the investigated compounds inhibited the catalytic activity of hAK1, yet with different efficiencies. Three dinucleoside polyphosphates showed IC 50 values below 1 µM, and the most significant inhibitory effect was observed for P 1-(5′-adenosyl) P5-(5′-adenosyl) pentaphosphate (Ap 5 A). To understand the observed differences in the inhibition efficiency of the tested dinucleoside polyphosphates, the molecular docking of these compounds to hAK1 was performed. Finally, we conducted a quantitative structure–activity relationship (QSAR) analysis to establish a computational prediction model for hAK1 modulators. Two PLS-regression-based models were built using kinetic data obtained from the AK1 activity analysis performed in both directions of the enzymatic reaction. Model 1 (AMP and ATP synthesis) had a good prediction power (R2 = 0.931, Q2 = 0.854, and MAE = 0.286), while Model 2 (ADP synthesis) exhibited a moderate quality (R2 = 0.913, Q2 = 0.848, and MAE = 0.370). These studies can help better understand the interactions between dinucleoside polyphosphates and adenylate kinase to attain more effective and selective inhibitors in the future. [ABSTRACT FROM AUTHOR]

• Two new rigid macrocyclic Schiff base ligands (L1 and L2) were synthesized. • X-ray analysis showed L1 as a double zwitterion. • Reactions of ligands with the Group VIB metal carbonyls. • Biological activities and molecular docking of reported compounds. Two new rigid macrocyclic Schiff base ligands incorporating acridine inter-crossing group [1,1′-(acridine-3,6-diylbis(azaneylylidene))bis(methaneylylidene))bis(naphthalen-2-ol), L1 , and N,N'-(acridine-3,6-diyl)bis(1-(quinolin-2-yl)methanimine), L2 , were synthesized and fully characterized. The X-ray single crystal analysis of L1 explored that the compound crystallized in a monoclinic crystal system with a space group P2 1 /c. The compound was crystalized with five water molecules. Interestingly, L1 occurred as a double zwitterion, where the hydrogen of the OH group of the hydroxynaphthalene transferred to the azomethine nitrogen to form NH+ and O− moieties with the presence of hydrogen bonding between them. Hirshfeld surface analysis of the L1 was also investigated. Reactions of the two ligands with the Group VIB metal carbonyls in air were investigated. In order to characterize the novel compounds, various analytical and spectroscopic methods were used. The analysis revealed that the complexes were formed as oxo derivatives with unique structural features. The presented compounds conducted fluorescence quenching investigations, viscosity evaluations, antimicrobial and antioxidant properties. It was concluded that the binding interaction with DNA was electrostatic binding mode rather than intercalative mode. Molecular docking of L1 and its complexes were investigated versus three macromolecular receptors (PDB: 4BJP , 1BQB and 1BNA). These targets were selected to compare the experimental biological data with the results of the docking analysis. [Display omitted] [ABSTRACT FROM AUTHOR]

• Thermal and microwave irradiation syntheses of some biologically active tetrahydrobenzo[ b ]thiophene derivatives. • X-ray single crystal and Hirshfeld surface studies of the precursor reagent. • DFT and molecular docking calculations. • Antimicrobial and cytotoxicity screening studies. • Correlation between the structure and the biological activity. Ethyl-2-amino-4,5,6,7-tetrahydrobenzo[ b ]thiophene-3-carboxylate (1) as a precursor derivative was used for the synthesis of variable heterocyclic compounds through its reactions with different reagents such as 9-anthraldehyde, 4-acetylbiphenyl, ethyl chloroacetate, ethyl benzoylacetate, chloroacetonitrile and diethyl malonate. Both conventional thermal and microwave irradiation techniques were used in the synthetic procedures. Molecular formulae and structures of the obtained derivatives were elucidated using different analytical and spectroscopic tools such as IR, 1H-, 13C-NMR as well as mass spectrometry. Variable structure features were observed for the products. The structure and crystal surface analysis of 1 were also obtained from the X-ray diffraction and Hirshfeld studies. Energy optimized structures of the reported compounds were performed by density functional theory (DFT/B3LYP) with the basis set 6-31 G and double zeta plus polarization (d,p). Quantum reactivity descriptors were calculated and correlated with their biological properties. The reported derivatives were analyzed for antimicrobial and cytotoxic inhibitions. The molecular docking studies of compounds were investigated as well. Structure and activity relationship of the reported compounds were correlated with the data of antimicrobial and cytotoxicity activity. [Display omitted] [ABSTRACT FROM AUTHOR]