Blue light induces DNA damage in normal human skin keratinocytes.

BACKGROUND: The generation of DNA damage by ultra-violet radiations (UV) is well established, and both the nature of the DNA lesions and their respective DNA repair pathways have largely been described. Besides UV rays, visible light constitutes a very important part of the sun spectrum where blue light is considered a significant contributor to premature aging. However, blue light-induced DNA damage has not been deeply explored yet. METHODS: In the present study, we assessed in human skin keratinocytes the DNA and chromosome damaging activities of blue light rays (415 nm) as well as their associated DNA repair mechanisms. RESULTS: Our results demonstrated that blue light induced dose-dependent DNA damage in human keratinocytes. Both oxidative and cyclobutane-pyrimidine-dimer (CPD) DNA lesions were generated. They were repaired through base excision repair (BER) and nucleotide excision repair (NER) pathways, respectively. Moreover, by using the micronucleus assay we demonstrated, for the first time, that a blue wavelength exerted a clastogenic/aneugenic effect in human keratinocytes, leading to chromosome aberration. CONCLUSION: We concluded that, in normal human keratinocytes, blue light creates genotoxic lesions which might accelerate or at least contribute to premature skin aging.

Synthesis, docking and evaluation of in vitro anti-inflammatory activity of novel morpholine capped ß-lactam derivatives.

This study reports the synthesis and biological investigation of three series of novel monocyclic ß-lactam derivatives bearing a morpholine ring substituent on the nitrogen. The resulting ß-lactam adducts were synthesized via Staudinger's [2 + 2]-ketene-imine cycloaddition reaction. New synthesized products were fully characterized by spectral data and elemental analyses, and then evaluated for anti-inflammatory activity toward human inducible nitric oxide synthase (iNOS) and cytotoxicity toward HepG2 cell line. The compounds 3e, 3h, 3k, 5c, 5f, 6c, 6d and 6f showed higher activity with anti-inflammatory ratio values of 38, 62, 51, 72, 51, 35, 55 and 99, respectively, in comparison to the reference compound dexamethasone having an anti-inflammatory ratio value of 32. Hence, these compounds can be considered as potent iNOS inhibitors. They also exhibited IC50 values of 0.48 ± 0.04 mM, 0.51 ± 0.01 mM, 0.22 ± 0.02 mM, 0.12 ± 0.00 mM, 0.25 ± 0.05 mM, 0.82 ± 0.07 mM, 0.44 ± 0.04 mM and 0.60 ± 0.04 mM, respectively, in comparison with doxorubicin (IC50 < 0.01 mM) against HepG2 cells, biocompatibility and nontoxic behavior. In silico prediction of drug-likeness characteristic indicated that the compounds are compliant with the Lipinski and Veber rules. Molecular docking experiments showed a good correlation between the experimental activity and the calculated binding affinity to human inducible nitric oxide synthase, the enzymatic target for the anti-inflammatory response.

Three-component synthesis of chromeno ß-lactam hybrids for inflammation and cancer screening.

Highly diastereoselective synthesis of chromeno ß-lactam hybrids was achieved by an efficient one-pot three-component reaction. With this procedure, the desired ß-lactam products were obtained in good yields and with exclusive cis stereoselection, by combining a variety of benzaldehydes, malononitrile, and either 5,5-dimethylcyclohexane-1,3-dione or 4-hydroxycoumarin in the presence of 1,4-diazabicyclo [2.2.2]octane under reflux conditions. These adducts were structurally characterized on the basis of IR, 1D and 2D NMR spectra, X-ray analysis, H-H COSY and H-C HSQC two-dimensional NMR experiments, and elemental analysis. Each of the synthesized compounds was screened for anti-inflammatory and anticancer activities. ß-Lactams 5b and 8b showed a 53.4 and 19.8 anti-inflammatory ratio, respectively, and 5b appeared more active than the well-known dexamethasone corticosteroid used for the treatment of rheumatoid and skin inflammation. ß-Lactams 5a, 5b, 5e, 5f, 5g, 8c, 8j and 8p also showed good antitumor activity against the SW1116 (colon cancer) cell line without notable cytotoxicity towards the HepG2 control cell line.

Claramines: A New Class Of Broad-Spectrum Antimicrobial Agents With Bimodal Activity.

The emergence of multidrug-resistant bacteria and pathogens has created an urgent need for the development of new antibiotics. Herein we report our investigations into the broad-spectrum activity of an easily prepared water-soluble polyaminosterol compound, namely claramine A1, against both drug-sensitive and drug-resistant Gram-negative and Gram-positive bacterial strains. We also report its peculiar mechanism of action, which differs from that of all the other well-known classes of antibiotics, toward Gram-negative and Gram-positive bacteria. Given their low cytotoxicity, this class of compounds based on claramine A1 could constitute an effective response to combat the emergence of multidrug-resistant bacteria and nosocomial diseases.