Mitochondrial genome damage associated with cigarette smoking

We have investigated the level of mitochondrial DNA (mtDNA) damage and deletions in bronchoalveolar lavage tissues from smokers and nonsmokers using quantitative, extra-long PCR and a "common" mtDNA deletion assay. Smokers had 5.6 times the level of mtDNA damage, 2.6 times the damage at a nuclear locus (beta-globin gene cluster), and almost 7 times the level of a 4.9-kb mtDNA deletion compared to nonsmokers, although the latter increase was not significant. Although both genomes (mitochondrial and nuclear) showed significantly increased levels of DNA damage in smokers (mtDNA P = 0.00072; beta-globin P = 0.0056), the relative differences were greatest in the mtDNA. Damage to the mtDNA may inhibit oxidative phosphorylation and, therefore, potentially cause or contribute to chronic lung disease and cancer. Consequently, the mtDNA may be a sensitive biomarker for environmentally induced genetic damage and mutation.     

One-Pot Synthesis and Antiproliferative Activity of Highly Functionalized Pyrazole Derivatives

A series of highly functionalized pyrazole derivatives has been prepared by a one-pot, versatile and regioselective procedure. Pyrazoles 1 – 29 were tested in cell-based assay to assess their antiproliferative activity against a panel of tumour cells. Additionally, the cytotoxicity of prepared compounds was evaluated against normal human fibroblasts. The antiproliferative activity of the synthesized molecules emerged to be affected by the nature of the substituents of the pyrazole scaffold and derivatives 21 – 23 proved to inhibit the growth of melanoma and cervical cancer cells. Compound 23 was identified as the most active derivative and docking simulations predicted its ability to interact with estrogen receptors.