Metal complexes of a pro-vitamin K3 analog phthiocol (2-hydroxy-3-methylnaphthalene-1,4-dione): synthesis, characterization, and anticancer activity.

The hydroxy analog of vitamin K3 (2-methylnaphthalene-1,4-dione) is known as phthiocol (2-hydroxy-3-methylnaphthalene-1,4-dione; pht). Both vitamin K3 and phthiocol possess anticancer and antihemorrhagic properties. Phthiocol is a noninnocent ligand and provides monodentate, bidentate, or tridentate coordination sites to metal ions. A series of transition metal complexes (Mn(II); 1 and 1A, Co(II); 2 and 2A, Ni(II); 3 and 3A, Cu(II); 4 and 4A, and Zn(II); 5 and 5A) are synthesized at 0 °C using sodium metal (1 to 5) and at 26 °C (1A to 5A). The chemical composition of the complexes obtained is of the type [M(phthiocolate)2(H2O)2]. At room temperature (26 °C), trans coordination of the phthiocolate ligand is achieved (1A through 5A), whereas at 0 °C and using sodium metal as a reductant, cis coordination is observed in Mn(II) complexes (1 and its methanol adduct 1B). A Na(I) complex of phthiocol, Na(pht), is isolated as a polymer. The ligand phthiocol and the complexes Na(pht), 1, 1A, and 3 crystallize in a monoclinic crystal system. X-ray structures reveal that the bond distances of coordinated phthiocol ligands are in the reduced naphthosemiquinone form in the complexes synthesized at 0 °C. The metal complexes of phthiocol (pht) were evaluated for their anticancer activity against MCF-7 (breast) and A549 (lung) cancer cell lines. Experiments like apoptosis, mitochondrial potential, reactive oxygen species (ROS) production, effect on the cell cycle, and cell proliferation were performed to compare selected complexes against both cell lines. The metal complexes of phthiocol synthesized at 0 °C showed substantial cytotoxic activity against MCF-7 and A549 cell lines. Further, effect of selected phthiocol complexes on peripheral blood mononuclear cells (PBMCs) was adventitious to realize their safety. Vitamin K3, phthiocol, and metal complex 4 successfully inhibited the enzymatic activity of human topoisomerase II. The multifunctionality of any anticancer agent influencing apoptosis, mitochondrial dysfunction, the effect on the cell cycle, and cell proliferation is crucial for defining the prognosis and precise treatment of cancer.

1H and 13C NMR chemical shifts of 2-n-alkylamino-naphthalene-1,4-diones.

1H as well as 13C chemical shifts of 32 compounds of C (3) substituted 2-(n-alkylamino)-3R-naphthalene-1,4-dione (where n-alkyl: methyl, to octyl, R = H, Cl, Br, and CH3) are investigated through 1H, 13C, DEPT, gDQCOSY, and gHSQCAD NMR experiments and M06-2X/6-311++G (d,p) density functional theory are discussed. Single crystal X-ray structure of Br-3, as well as 18 different derivatives of naphthalene-1,4-diones, are revealed for its inter and intra-molecular hydrogen bonding interactions.

Coordination polymers of CdII and PbII derived from bipyridine-glycoluril: influence of metal-ion size and counter-ions.

Two new one-dimensional (1D) coordination polymers (CPs), namely catena-poly[[[aquacadmium(II)]-bis(µ-4b,5,7,7a-tetrahydro-4b,7a-epiminomethanoimino-6H-imidazo[4,5-f][1,10]phenanthroline-6,13-dione)] bis(perchlorate) dihydrate], {[Cd(C14H10N6O2)2(H2O)](ClO4)2·2H2O}n or {[Cd(BPG)2(H2O)](ClO4)2·2H2O}n, 1, and catena-poly[[lead(II)-bis(µ-4b,5,7,7a-tetrahydro-4b,7a-epiminomethanoimino-6H-imidazo[4,5-f][1,10]phenanthroline-6,13-dione)] bis(perchlorate) dihydrate], {[Pb(C14H10N6O2)2](ClO4)2·2H2O}n or {[Pb(BPG)2](ClO4)2·2H2O}n, 2, have been synthesized using bipyridine-glycoluril (BPG; systematic name: 4b,5,7,7a-tetrahydro-4b,7a-epiminomethanoimino-6H-imidazo[4,5-f][1,10]phenanthroline-6,13-dione), a urea-fused tecton, in a mixed-solvent system. The CdII ion in 1 is heptacoordinated and the PbII ion in 2 is hexacoordinated, with the CdII ion adopting a pentagonal bipyramidal geometry and the PbII ion adopting a distorted octahedral geometry. Both CPs form infinite linear chain structures which are hydrogen bonded to each other leading to the formation of three-dimensional supramolecular network structures. Topological analysis of CPs 1 and 2 reveals that the structures exhibit 1D chain-like arrangements in an AB-AB sequence and shows platonic uniform 2-connected uninodal topologies. Furthermore, a comparative analysis of a series of structures based on the BPG ligand indicates that the size of the metal ion and the types of counter-ions used have a great influence on the resulting frameworks and properties.

Iminosugars Spiro-Linked with Morpholine-Fused 1,2,3-Triazole: Synthesis, Conformational Analysis, Glycosidase Inhibitory Activity, Antifungal Assay, and Docking Studies.

Synthesis of iminosugars 1, 2, 3a, and 4a and N-alkyl (ethyl, butyl, hexyl, octyl, decyl, and dodecyl) derivatives 3b-g and 4b-g spiro-linked with morpholine-fused 1,2,3-triazole is described. Conformation of the piperidine ring in each spiro-iminosugar was evaluated by 1H NMR spectroscopy, and conformational change in N-alkylated compounds 4b-g with respect to parent spiro-iminosugar 4a is supported by density functional theory calculations. Out of 16 new spiro-iminosugars, the spiro-iminosugars 3a (IC50 = 0.075 µM) and 4a (IC50 = 0.036 µM) were found to be more potent inhibitors of α-glucosidase than the marketed drug miglitol (IC50 = 0.100 µM). In addition, 3a (minimum inhibition concentration (MIC) = 0.85 µM) and 4a (MIC = 0.025 µM) showed more potent antifungal activity against Candida albicans than antifungal drug amphotericin b (MIC = 1.25 µM). In few cases, the N-alkyl derivatives showed increase of α-glucosidase inhibition and enhancement of antifungal activity compare to the respective parent iminosugar. The biological activities were further substantiated by molecular docking studies.

Conformational modulation of peptides using ß-amino benzenesulfonic acid ((S)Ant).

This communication describes the utility of a conformationally restricted aromatic ß-amino acid (2-aminobenzenesulfonic acid, (S)Ant) inducing various folding interactions in short peptides. Sandwiching (S)Ant between diverse amino acid residues was shown to form robust folded architectures featuring a variety of H-bonded networks, suggesting its utility in inducing peptide folding.