Azithromycin has become famous in the last two years, not for its main antimicrobial effect, but for its potential use as a therapeutic agent for COVID-19 infection. Initially, there were some promising results that supported its use, but it has become clear that scientific results are insufficient to support such a positive assessment. In this review we will present all the literature data concerning the activity of azithromycin as an antimicrobial, an anti-inflammatory, or an antivirus agent. Our aim is to conclude whether its selection should remain as a valuable antivirus agent or if its use simply has an indirect therapeutic contribution due to its antimicrobial and/or immunomodulatory activity, and therefore, if its further use for COVID-19 treatment should be interrupted. This halt will prevent further antibiotic resistance expansion and will keep azithromycin as a valuable anti-infective therapeutic agent.

The impact of metals bioaccumulation in marine organisms is a subject of intense investigation. This study was designed to determine the association between oxidative stress induced by seawater enriched with trace metals and protein synthesis using as a model the mussels Mytilus galloprovincialis. Mussels were exposed to 40 μg/L Cu, 30 μg/L Hg, or 100 μg/L Cd for 5 and 15 days, and the pollution effect was evaluated by measuring established oxidative biomarkers. The results showed damage on the protein synthesis machine integrity and specifically on translation factors and ribosomal proteins expression and modifications. The exposure of mussels to all metals caused oxidative damage that was milder in the cases of Cu and Hg and more pronounced for Cd. However, after prolonged exposure of mussels to Cd (15 days), the effects receded. These changes that perturb protein biosynthesis can serve as a great tool for elucidating the mechanisms of toxicity and could be integrated in biomonitoring programs.

Over the last years, we have been focused on chloramphenicol conjugates that combine in their structure chloramphenicol base with natural polyamines, spermine, spermidine and putrescine, and their modifications. Conjugate 3, with spermidine (SPD) as a natural polyamine linked to chloramphenicol base, showed the best antibacterial and anticancer properties. Using 3 as a prototype, we here explored the influence of the antibacterial and anticancer activity of additional benzyl groups on N1 amino moiety together with modifications of the alkyl length of the aminobutyl fragment of SPD. Our data demonstrate that the novel modifications did not further improve the antibacterial activity of the prototype. However, one of the novel conjugates (4) showed anticancer activity without affecting bacterial growth, thus emerging as a promising anticancer agent, with no adverse effects on bacterial microflora when taken orally.

To combat the dangerously increasing pathogenic resistance to antibiotics, we developed new pharmacophores by chemically modifying a known antibiotic, which remains to this day the most familiar and productive way for novel antibiotic development. We used as a starting material the chloramphenicol base, which is the free amine group counterpart of the known chloramphenicol molecule antibiotic upon removal of its dichloroacetyl tail. To this free amine group, we tethered alpha- and beta-amino acids, mainly glycine, lysine, histidine, ornithine and/or beta-alanine. Furthermore, we introduced additional modifications to the newly incorporated amine groups either with protecting groups triphenylmethyl- (Trt) and tert-butoxycarbonyl- (Boc) or with the dichloroacetic group found also in the chloramphenicol molecule. The antimicrobial activity of all compounds was tested both in vivo and in vitro, and according to the results, the bis-dichloroacetyl derivative of ornithine displayed the highest antimicrobial activity both in vivo and in vitro and seems to be a dynamic new pharmacophore with room for further modification and development.

In a previous study published by our group, successful modification of the antibiotic chloramphenicol (CHL) was reported, which was achieved by replacing the dichloroacetyl tail with alpha and beta amino acids, resulting in promising new antibacterial pharmacophores. In this study, CHL was further modified by linking the basic amino acids lysine, ornithine, and histidine to the primary hydroxyl group of CHL via triazole, carbamate, or amide bonding. Our results showed that while linking the basic amino acids retained antibacterial activity, it was somewhat reduced compared to CHL. However, in vitro testing demonstrated that all derivatives were comparable in activity to CHL and competed for the same ribosomal binding site with radioactive chloramphenicol. The amino acid–CHL tethering modes were evaluated either with carbamate (7, 8) derivatives, which exhibited higher activity, or with amide- (4–6) or triazole-bridged compounds (1–3), which were equally potent. Our findings suggest that these new pharmacophores have potential as antimicrobial agents, though further optimization is needed.