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The growing resistance of microorganisms towards antibiotics has become a serious global problem. Therapeutics with novel chemical scaffolds and/or mechanisms of action are urgently needed to combat infections caused by multidrug resistant pathogens, including bacteria, fungi and viruses. Development of novel antimicrobial agents is still highly dependent on the discovery of new natural products. At present, most antimicrobial drugs used in medicine are of natural origin. Among the natural producers of bioactive substances, Actinobacteria continue to be an important source of novel secondary metabolites for drug application. In this review, the authors report on the bioactive antimicrobial secondary metabolites of Actinobacteria that were described between 2011 and April 2018. Special attention is paid to the chemical scaffolds, biological activities and origin of these novel antibacterial, antifungal and antiviral compounds. Arenimycin C, chromopeptide lactone RSP 01, kocurin, macrolactins A1 and B1, chaxamycin D as well as anthracimycin are regarded as the most effective compounds with antibacterial activity. In turn, the highest potency among selected antifungal compounds is exhibited by enduspeptide B, neomaclafungins A-I and kribelloside D, while ahmpatinin iBu, antimycin A1a, and pentapeptide 4862F are recognized as the strongest antiviral agents.

A new metabolite, cyclic dipeptide, cis-(3S,8aS)-3-(3,4-dihydroxybenzyl)hexahydropyrrolo[1,2-a]pyrazine-1,4-dione, named JS-3 was isolated from Streptomyces sp. 8812 fermentation broth. Its chemical structure was established by means of spectroscopic analysis. A wide-range-screening study, which included inhibition assay of DD-carboxypeptidase/transpeptidase activity, determination of antibacterial, antifungal, and antiproliferative activities as well as free-radical scavenging was performed. To authors knowledge, this is the first isolation of such compound from natural sources and the first one from bacteria, Streptomyces.

Four new ferrocenyl-flavone complexes were obtained via palladium-catalyzed Heck cross-coupling reactions; (E)-6-ferrocenylvinyl-chromen-4-one (4), (E)-6-ferrocenylvinyl-2-methyl-chromen-4-one (5), (E)-6-ferrocenylvinyl-2-phenyl-chromen-4-one (6) and (E)-6-ferrocenylvinyl-chromen-4-one-3-propionic acid (7). All compounds were characterized by 1H NMR, 13C NMR, IR spectroscopy, high resolution-MS, elemental analysis and cyclic voltammetry. The molecular structure of derivatives 4 and 6 was also confirmed by X-ray crystallography. The biological activity of the complexes was rationalized on the basis of their anticancer and antibacterial properties. The anticancer activity of ferrocenyl-flavones 4–7 against established human cell lines derived from hematological and solid tumors has been evaluated in vitro. The following cell lines were investigated: MCF-7 (estrogen receptor-responsive breast adenocarcinoma), MDA-MB-231 (estrogen receptor-negative breast adenocarcinoma), HepG2 (hepatocellular carcinoma) and CCRF-CEM (T lymphoblast-like polymorph cells). All investigated ferrocenyl-flavones show cytotoxicity against CCRF-CEM cell line. The antibacterial activity of the four ferrocenyl-flavones against Gram-positive methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), vancomycin-resistant S. aureus (VRSA) and Staphylococcus epidermidis bacterial strains was determined. Our experiments show antibacterial activity for the carboxylic acid derivative 7 against all tested Gram-positive bacterial strains while no activity was detected for the ferrocene-free 6-bromo-chromen-4-one-3-propionic acid.

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.

Secondary metabolites obtained from Actinomycetales provide a potential source of many new antibacterial, antitumour, antifungal, antiviral, antiparasitic compounds and others. The majority of discovered substances are widely used as medicines for combating multidrug-resistant Gram-positive and Gram-negative bacterial strains, as well as in veterinary practice, agriculture and industry. Members of the Streptomyces genus are outstanding producers of already known secondary metabolites. In our study we isolated a new metabolite from Streptomyces badius fermentation broth. This compound, 2-acetamido-5-hydroxybenzoic acid (1) was already described in literature, however, not yet discovered as Streptomyces badius product. The compound was firstly isolated from fermentation broth and purified by chromatography methods (ion exchange resin DowexWX40, Solid Phase Extraction C18 Polar Plus; HPLC, dC18). Then, the chemical structure of metabolite was determined by 1H NMR, 13C NMR and 2D homo- and heteronuclear (1H-13C HSQC, 1H-13C HMBC) NMR. The molecular formula of (1), C9H9NO4 was identified by high resolution ESI-MS. The chemical structure was analyzed by the UV and IR methods, as well. Biological activities of 2-acetamido-5-hydroxybenzoic acid were evaluated. The compound shows moderate DD-peptidase 64-575 inhibitory activity as well as antioxidative properties (ABTS radical scavenging). Such chemical moiety may serve as model compound for further modern drug discovery and be a source of active substance in anti-ageing cosmetics.

We report on the synthesis of ferrocenyl-ampicillin and ferrocenyl-6-aminopenicillinic acid bioconjugates. Title compounds were characterized by (1)H NMR, IR, MS and elemental analysis. These novel ferrocenyl-antibiotic conjugates were also investigated by cyclic voltammetry (CV). Ferrocenyl-ampicillin complexes revealed reversible uncomplicated oxidation whereas ferrocenyl-6-aminopenicillinic acid derivatives were found to exhibit adsorption waves in cathodic scans. Antibacterial activities of our ferrocenyl-antibiotic conjugates against Gram-positive methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), vancomycin-resistant S. aureus (VRSA) and Staphylococcus epidermidis bacterial strains were determined. Our experiments show significant antibacterial activity of ferrocenyl-6-aminopenicillinic acid bioconjugates against the bacterial strains tested. Contrary to that ferrocenyl-ampicillin derivatives were inactive. The inhibitory effects on the dd-carboxypeptidase 64-575 II exerted by our ferrocenyl-6-aminopenicillinic acid bioconjugates were established in the low nanomolar range. The tumor cell growth inhibition of representative ferrocenyl-ampicillin and ferrocenyl-6-aminopenicillinic acid bioconjugates against MCF-7 breast adenocarcinoma and HT-29 colon carcinoma cell lines were studied in vitro. Similar to the antibacterial activity tests the assays in tumor cells revealed significant antiproliferative effects exerted by ferrocenyl-6-aminopenicillinic acid bioconjugates.

Secondary 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.

The incidence of candidiasis among immunocompromised patients and emergence of antimycotics resistant strains has increased significantly. The aims of this study were: to examine the in vitro activity of antimycotics and biocides against Candida clinical isolates; to detect cross-resistance of fungi to these preparations and to estimate whether disinfectants applied in hospital areas are active against clinical Candida isolates. In vitro susceptibility of 102 Candida isolates to eight antimycotics was examined by Etest and ATB Fungus. Sensitivity of these strains to four disinfectants and an antiseptic agent was tested according to EN 1275:2005. Amphotericin B, caspofungin and 5-fluorocytosine were the most effective antimycotics against all Candida isolates. Resistance to itraconazole and fluconazole was observed among C. krusei and C. glabrata. The MICs (Minimal Inhibitory Concentrations) for ketoconazole, voriconazole and posaconazole against Candida albicans ranged: 0.003 - >32 μg/ml and one strain was resistant to three agents tested. All analysed Candida strains were sensitive to biocides containing either chlorine, aldehyde, alcohol mixtures, glucoprotamin or chlorhexidine gluconate with isopropanol. Sensitivity to these agents was observed at concentrations lower than those concentrations recommended by manufacturers to achieve proper biocidal activity to those preparations. Our data suggest that these disinfectants can be effectively applied in clinical wards to prevent nosocomial Candida infections.

The [2+2]cycloaddition of chlorosulfonyl isocyanate to vinyl and (Z)-propenyl ethers derived from the 2-O-sulfonylated (R)- and (S)-1-(furyl-2′)-1,2-ethanediols furnished the 4-alkoxy-azetidin-2-ones with a good to moderate stereoselectivity. The intramolecular alkylation of the β-lactam nitrogen atom led to the corresponding 3-(furyl-2′)- and 6-methyl-3-(furyl-2′)-clavams. The transformation of the furyl residue into an alkoxycarbonyl group led to clavams related to the natural compounds. The synthesized clavams exhibited moderate inhibitory activities against DD-peptidase 64-575 and β-lactamase (penase) as well as antifungal activities.

The [2+2]cycloaddition of chlorosulfonyl isocyanate to vinyl and (Z)-propenyl ethers derived from the 2-O-sulfonylated (R)- and (S)-1-(furyl-2')-1,2-ethanediols furnished the 4-alkoxy-azetidin-2-ones with a good to moderate stereoselectivity. The intramolecular alkylation of the beta-lactam nitrogen atom led to the corresponding 3-(furyl-2')- and 6-methyl-3-(furyl-2')-clavams. The transformation of the furyl residue into an alkoxycarbonyl group led to clavams related to the natural compounds. The synthesized clavams exhibited moderate inhibitory activities against DD-peptidase 64-575 and beta-lactamase (penase) as well as antifungal activities.