Two 2-amino-1,3,4-thiadiazoles containing phenolic hydroxyl groups were combined with different carboxylic acid chlorides giving sixteen amide derivatives with good antioxidant and antiproliferative potential. The compound 3'c with an adamantane ring displayed excellent DPPH radical scavenging activity and good cytotoxic activity against human acute promyelocytic leukemia HL-60 cells, while 1,3,4-thiadiazole 3'h with 4-chlorophenyl moiety was found to be the most effective in inhibition of survival of lung carcinoma A549 cells. All examined thiadiazoles except 3a and 3'a exerted higher cytotoxic activities on A549 and HL-60 cancer cells when compared with normal fibroblasts MRC-5, pointing to selectivity in their antiproliferative action. Some of the most active novel compounds 3c, 3'c, 3'g and 3'h induced significant increase in the percentage of HL-60 cells in the subG1 cell cycle phase in comparison with the control cells. The induction of cell death in HL-60 cells by these compounds was at least partially dependent on activation of caspase-3 and caspase-8. The compounds 3c and 3'c exerted strong antiangiogenic activity. Furthermore, compounds 3c, 3'c, 3'g and 3'h showed the ability to down-regulate the MMP2 and VEGFA expression levels in the treated HL-60 cells when compared with the control cell samples.

No abstract

Eight 1,3,4-oxadiazole derivatives containing phenolic acid moieties (7a-h) and eight of their diacylhydrazine precursors (6a-h) were synthesized, characterized using spectroscopic methods and examined by scavenging of stable DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals. The most potent phenolic 1,3,4-oxadiazoles showed better DPPH scavenging activity in comparison with their corresponding diacylhydrazine precursors as a result of participation of both aromatic rings and a 1,3,4-oxadiazole moiety in resonance stabilization of the formed phenoxyl radical. Four diacylhydrazines (6d, 6e, 6g, and 6h) and four 1,3,4-oxadiazoles (7d, 7e, 7g and 7h) with the best DPPH scavenging activity, were chosen for further evaluation of their antioxidant potential through various assays. The investigated compounds exerted pronounced ABTS radical scavenging capacity, moderate to good H 2 O 2 scavenging properties and strong ferric ion reducing capacity. Further in vitro evaluation of the antioxidant properties of the most active compounds demonstrated their protective effects in normal lung fibroblasts MRC-5 against hydrogen peroxide induced oxidative stress. Diacylhydrazine 6h increased two times the activity of glutathione peroxidase in treated cells in comparison with a control sample and did not affect the superoxide dismutase activity.

No abstract

No abstract

No abstract

If λ 1 > λ 2 ≥ λ 3 ≥ ··· ≥ λ n are the eigenvalues of the molecular graph, then the Estrada index, a recently conceived molecular structure-descriptor is EE = n ∑ i=1 e λ i . The same alkanes, whose molecular graphs have extremal Wiener indices and λ 1 , are shown to be also extremal with regard to the Estrada index.

Five pentacoordinate copper(II) complexes with 2‐acetylpyridine or di(2‐pyridyl) ketone 1‐adamantoyl hydrazone ligands (Adpy and Addpy, respectively) of the formulae [CuCl2(Adpy)] (1), [Cu2(μ‐Cl)2(Adpy‐H)2] (2), [Cu(NCS)2(Adpy)] (3), [Cu2(μ‐Cl)2(Addpy‐H)2] (4), and [Cu2(NCS)2(μ‐Addpy‐H)2] (5) were synthesized and characterized by spectral, electrochemical, and X‐ray structural analysis. Flow cytometry and morphological analysis confirmed that the copper(II) complexes 2 and 5 induced accumulation of a sub‐G1 phase population, and fluorescence microscopy indicated the presence of large cells in apoptosis. The interaction of the copper(II) complexes with calf thymus DNA (CT‐DNA) was monitored by changes in their UV/Vis spectra. The observed intrinsic binding constants for 2 and 5 (Kb = 1.77 × 106 and 3.58 × 106 M–1, respectively) together with ethidium displacement fluorescence experiments indicate intercalative binding. Complexes 2 and 5 showed nuclease activity against pUC19 plasmid DNA.