AbstractSecondary metabolites obtained from Actinomycetales provide a potential source of many novel compounds with antibacterial, antitumour, antifungal, antiviral, antiparasitic and other properties. The majority of these compounds are widely used as medicines for combating multidrug-resistant Gram-positive and Gram-negative bacterial strains. Members of the genus Streptomyces are profile producers of previously-known secondary metabolites. Actinomycetes have been isolated from terrestrial soils, from the rhizospheres of plant roots, and recently from marine sediments. This review demonstrates the diversity of secondary metabolites produced by actinomycete strains with respect to their chemical structure, biological activity and origin. On the basis of this diversity, this review concludes that the discovery of new bioactive compounds will continue to pose a great challenge for scientists.

A new family of metallocene–uracil conjugates, including [3-(N1-uracilyl)-1-(ferrocenyl)]propene (2c), [3-(N1-thyminyl)-1-(ferrocenyl)]propene (3c), [3-(N1-(5-fluorouracilyl))-1-(ferrocenyl)]propene (4c), and [3-(N1-uracilyl)-1-(ruthenocenyl)]propene (5c), was obtained in three steps from (3-chloropropionyl)ferrocene and (3-chloropropionyl)ruthenocene, respectively. The complexes 2c–5c and their intermediates 2a–5a and 2b–5b were characterized by NMR and infrared spectroscopy, mass spectrometry, and elemental analysis. The molecular structures of the intermediates 2b and 4a were determined by single-crystal X-ray structure analysis. In the solid state, two molecules of 2b or 4a form a dimeric structure, which is held together by strong hydrogen bonds. Compounds 2c–5c were also studied by cyclic voltammetry (CV). The ferrocenyl–uracil derivatives 2c–4c revealed reversible uncomplicated oxidations, whereas the cyclic voltammogram of the ruthenocenyl derivative 5c showed an irreversible oxidation. Compounds 2c–5c were tested for their antiproliferative activity against human MCF-7 breast adenocarcinoma and HT-29 colon carcinoma cells. Compounds 3c–5c were moderately active against MCF-7 cancerous cells. Atomic absorption spectroscopy measurements on compound 5c revealed that the ruthenocenyl derivative is taken up by HT-29 cells in a time-dependent manner. However, the ruthenium cellular level remains relatively low. Compounds 2a–5a were also tested against Gram-positive methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA) and Staphylococcus epidermidis bacterial strains. Compound 4a showed significant antibacterial activity against all bacterial strains, while compounds 2a and 3b were only moderately active. No antibacterial activity was found for the ruthenocenyl derivative 5a.

We have determined a 1.18 Å resolution X-ray crystal structure of a novel ruthenocenyle-6-aminopenicillinic acid in complex with CTX-M β-lactamase, showing unprecedented details of interactions between ruthenocene and protein. As the first product complex with an intact catalytic serine, the structure also offers insights into β-lactamase catalysis and inhibitor design.

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Bacterial resistance to commonly used antibiotics is constantly increasing. Bacteria particularly dangerous for human life are methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium and fluoroquinolone-resistant Pseudomonas aeruginosa. Hence, there is an incessant need for developing compounds with new modes of action and seeking alternate drug targets. In this review, the authors discuss the current situation of antibacterial medicines and present data on new antibiotic targets. Moreover, alternatives to antibiotics, such as bacteriophages, antimicrobial peptides and monoclonal antibodies, are presented. The authors also draw attention to the valuable features of natural sources in developing antibacterial compounds. The need to prevent and control infections as well as the reasonable use of currently available antibiotics is also emphasized.

Novel polyfunctional small amphiphilic peptide dendrimers characterized by incorporation of a new core compounds – tris-amino acids or tetrakis-amino alcohols that originated from a series of basic amino acids – were efficiently synthesized. These new core elements yielded molecules with multiple branching and (+5)/(+6) charge at the 1-st dendrimer generation. Dendrimers exhibited significant antimicrobial potency against Gram(+) and Gram(-) strains involving also multiresistant reference strains (S. aureus ATCC 43300 and E. coli ATCC BAA-198). In addition, high activity against fungi from the Candida genus was detected. More charged and more hydrophobic peptide dendrimers expressed hemolytic properties.

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