Due to the steady rise of multidrug-resistant pathogenic bacteria worldwide, it is critical to develop novel antibacterial drugs. This article presents chimeric antisense oligonucleotides that inhibit the bacterial growth of Staphylococcus aureus, one of the most frequent causes of hospital-acquired infections. The chimeric antisense oligonucleotides have a combination of first- and second-generation chemical modification. To deliver the antisense oligonucleotides into a cell, we apply a cell-penetrating oligopeptide attached to them. We have performed complete bioinformatics analyses of the glmS ribozyme present in S. aureus and its essential role in the biochemical pathway of glucosamine-6-phosphate synthesis. Besides, we have analyzed the bacteria for alternative metabolic pathways, such as the nagA gene. The first antisense oligonucleotide explicitly targets the glmS riboswitch, while the second explicitly targets the nagA mRNA. We have evaluated that combined, the antisense oligonucleotides block the synthesis of glucosamine-6-phosphate entirely and inhibit the bacterial growth of S. aureus. However, the glmS riboswitch targeting the antisense oligonucleotide is sufficient to inhibit the growth of S. aureus with a MIC80 of 5 μg/mL. The glmS ribozyme is a very suitable target for antibacterial drug development with antisense oligonucleotides.

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Two new families of Cu(II) and Co(II) mononuclear complexes with mixed ligands, [Cu(VanTrpt)(bipy)]ÁMeOH (CuVanTrpt), [Cu(VanSer)(bipy)]Á4H 2 O (CuVanSer), [Cu(VanTyr)(bipy)]ÁH 2 O (CuVanTyr), [Cu(VanThr)(bipy)]Á MeOH (CuVanThr), [Co(VanTrpt)(bipy)(OH 2 )]ÁH 2 OÁMeOH (CoVanTrpt), [Co(VanSer)(bipy)(OH 2 )]ÁMeOH (CoVanSer), [Co(VanTyr)(bipy)(OH 2 )]Á 3H 2 OÁMeOH (CoVanTyr), and [Co(VanThr)(bipy)(OH 2 )] (CoVanThr), (VanX are Schiff base proligands resulted from the condensation of o-vanillin with D,L-tryptophan (VanTrpt), L-serine (VanSer), L-tyrosine (VanTyr), and L-threonine (VanThr), respectively, and bipy is 2,2 0 -bipyridine), have been obtained and characterized on the basis of elemental analysis, magnetic measurements, and spectral data (FT-IR and UV-Vis-Nir spectroscopy). Crystal structures of CuVanTrpt, CuVanSer, and CuVanTyr have been solved by single-crystal X-Ray diffraction. Biological evaluation revealed that they are cytotoxic in HeLa (human carcinoma of the uterine cervix) and LSR-SF-SR (rat sarcoma induced by Rous sarcoma virus strain Schmidt-Ruppin) cells, showing an enhancement of cytotoxicity dependent of concentration and treatment time. The most pronounced cytotoxic effect is expressed by CuVanSer and CoVanSer. Various cytopathological changes of both types of cancer cells were observed after treatment with Cu(II) and Co(II) complexes for 72 h at concentrations of 100 and 200 μg ml À1 . LSR-SF-SR cells were found to be relatively more sensitive to the cytotoxic effect of the complexes investigated as compared to HeLa cells. K E Y W O R D S amino acids, cobalt(II) complexes, copper(II) complexes, cytotoxic activity, Schiff base proligands Desislav Dinev and Daniela C. Culita contributed equally to the manuscript.