DNA intercalative 4-butylaminopyrimido4',5':4,5]thieno(2,3-b)quinoline induces cell cycle arrest and apoptosis in leukemia cells

DNA intercalators are one of the interesting groups in cancer chemotherapy. The development of novel anticancer small molecule has gained remarkable interest over the last decade. In this study, we synthesized and investigated the ability of a tetracyclic-condensed quinoline compound, 4-butylaminopyrimido4',5':4,5]thieno(2,3-b)quinoline (BPTQ), to interact with double-stranded DNA and inhibit cancer cell proliferation. Circular dichroism, topological studies, molecular docking, absorbance, and fluorescence spectral titrations were employed to study the interaction of BPTQ with DNA. Cytotoxicity was studied by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assay. Further, cell cycle analysis by flow cytometry, annexin V staining, mitochondrial membrane potential assay, DNA fragmentation, and western blot analysis were used to elucidate the mechanism of action of BPTQ at the cellular level. Spectral, topological, and docking studies confirmed that BPTQ is a typical intercalator of DNA. BPTQ induces dose-dependent inhibitory effect on the proliferation of cancer cells by arresting cells at S and G2/M phase. Further, BPTQ activates the mitochondria-mediated apoptosis pathway, as explicated by a decrease in mitochondrial membrane potential, increase in the Bax:Bcl-2 ratio, and activation of caspases. These results confirmed that BPTQ is a DNA intercalative anticancer molecule, which could aid in the development of future cancer therapeutic agents.

Synthesis and evaluation of 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazoles as anti-cancer agents

A series of 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazoles 9a-j were obtained via multistep synthesis from hydroxybenzophenones 4a-e. The cytotoxicity of compounds 9a-j was evaluated against human leukemia cell lilies (K562 and CEM). The compounds exhibited moderate to good anti-cancer activity with compounds 9b and 9i having a chloro group exhibiting the best activity (IC50 = 10 mu M). Compound 9i exhibited activity against both the cell lines and 9b only exhibited activity against CEM. Further, a lactate dehydrogenase (LDH) assay and DNA fragmentation studies of the compounds 9a-j were also performed. (C) 2013 Elsevier Masson SAS. All rights reserved.

Simultaneous presence of fhs and purT genes is disadvantageous for the fitness of Escherichia coli growth

In bacteria, alternate mechanisms are known to synthesize N-10-formyltetrahydrofolate (N10-formyl-THF) and formyl glycinamide ribotide (fGAR), which are important in purine biosynthesis. In one of the mechanisms, a direct transfer of one carbon unit from formate allows Fhs to convert tetrahydrofolate to N-10-formyl-THF, and PurT to convert glycinamide ribotide (GAR) to fGAR. Our bioinformatics analysis of fhs and purT genes (encoding Fhs and PurT) showed that in a majority of bacteria (similar to 94%), their presence was mutually exclusive. A large number of organisms possessing fhs lacked purT and vice versa. The phenomenon is so penetrating that even within a genus (Bacillus) if a species possessed fhs it lacked purT and vice versa. To investigate physiological importance of this phenomenon, we used Escherichia coli, which naturally lacks fhs (and possesses purT) as model. We generated strains, which possessed fhs and purT genes in singles or together. Deletion of purT from E. coli in the presence or absence of fhs did not confer a detectable growth disadvantage in pure cultures. However, growth competition assays revealed that the strains possessing either of the single genes outcompeted those possessing both the genes suggesting that mutual exclusion of purT and fhs in organisms confers fitness advantage in mixed cultures.

Order-disorder phase transition and multiferroic behaviour in a metal organic framework compound (CH3)(2)NH2Co(HCOO)(3)

We have investigated the multiferroic and glassy behaviour of metal-organic framework (MOF) material (CH3)(2)NH2Co(CHOO)(3). The compound has perovskite-like architecture in which the metal-formate forms a framework. The organic cation (CH3)(2)NH2+ occupies the cavities in the formate framework in the framework via N-H center dot center dot center dot O hydrogen bonds. At room temperature, the organic cation is disordered and occupies three crystallographically equivalent positions. Upon cooling, the organic cation is ordered which leads to a structural phase transition at 155 K. The structural phase transition is associated with a para-ferroelectric phase transition and is revealed by dielectric and pyroelectric measurements. Further, a PE hysteresis loop below 155 K confirms the ferroelectric behaviour of the material. Analysis of dielectric data reveal large frequency dispersion in the values of dielectric constant and tan delta which signifies the presence of glassy dielectric behaviour. The material displays a antiferromagnetic ordering below 15 K which is attributed to the super-exchange interaction between Co2+ ions mediated via formate linkers. Interestingly, another magnetic transition is also found around 11 K. The peak of the transition shifts to lower temperature with increasing frequency, suggesting glassy magnetism in the sample. (C) 2016 AIP Publishing LLC.