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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