Maria Jolanta Milewska

Systemic mycoses, caused mainly in the immunocompromised patients by Candida spp. yeasts, especially C. albicans, are difficult to treat because of the small set of effective chemotherapeutics, eme...

One of the reasons for the decreasing effectiveness of modern antimicrobial chemotherapy and the increasing resistance of pathogenic microorganisms to drugs is a hampered access of active agents to intracellular targets, due to the problems with crossing the biological membrane barriers. This article discusses the possibilities and methods of using oligopeptides that penetrate cell membranes by simple diffusion, endocytosis or using active transport systems, as molecular carriers for the construction of antimicrobial conjugates, following the Trojan Horse strategy. The basis for the discussion and conclusions is a critical review of the literature from 1970 to 2025, searched in Web of Science, PubMed and Scopus, with a strong emphasis on examples from the last decade. Application of short peptides transported by microbial oligopeptide transport systems, cell penetrating peptides and antimicrobial peptides as molecular carriers may give rise to novel antimicrobial conjugates, able to overcome microbial resistance, as well as to enhancement of antimicrobial potential and broadening of antimicrobial spectrum of existing drugs, especially against intracellular microbial pathogens.

Lanosterol is the crucial intermediate in ergosterol biosynthesis in fungi. A number of derivatives of natural or synthetic origin of these sterols are portrayed in this review. For the synthetic derivatives, strategies of their syntheses are presented. Biological activities of lanosterol and ergosterol derivatives include antimicrobial, especially antifungal action, anticancer and antiviral effects but also anti‐inflammatory and anti‐allergic potential. The most promising seems to be the anticancer potential of peroxides, epoxides, and keto‐ derivatives of both sterols.

Greenness metrics for comparative, comprehensive and simple assessment of organic syntheses processes.

Structures of several dozen of known antibacterial, antifungal or antiprotozoal agents are based on the amino acid scaffold. In most of them, the amino acid skeleton is of a crucial importance for their antimicrobial activity, since very often they are structural analogs of amino acid intermediates of different microbial biosynthetic pathways. Particularly, some aminophosphonate or aminoboronate analogs of protein amino acids are effective enzyme inhibitors, as structural mimics of tetrahedral transition state intermediates. Synthesis of amino acid antimicrobials is a particular challenge, especially in terms of the need for enantioselective methods, including the asymmetric synthesis. All these issues are addressed in this review, summing up the current state‐of‐the‐art and presenting perspectives fur further progress.

A molecular umbrella composed of two O-sulfated cholic acid residues was applied for the construction of conjugates with cispentacin, containing a “trimethyl lock” (TML) or o-dithiobenzylcarbamoyl moiety as a cleavable linker. Three out of five conjugates demonstrated antifungal in vitro activity against C. albicans and C. glabrata but not against C. krusei, with MIC₉₀ values in the 0.22–0.99 mM range and were not hemolytic. Antifungal activity of the most active conjugate 24c, containing the TML–pimelate linker, was comparable to that of intact cispentacin. A structural analogue of 24c, containing the Nap-NH₂ fluorescent probe, was accumulated in Candida cells, and TML-containing conjugates were cleaved in cell-free extract of C. albicans cells. These results suggest that a molecular umbrella can be successfully applied as a nanocarrier for the construction of cleavable antifungal conjugates.

The review presents synthetic aspects of carbon nanotube and dendrimer conjugation with drugs and other bioactive molecules.

Background: It is assumed that the unfavorable selective toxicity of an antifungal drug Amphotericin B (AmB) can be improved upon chemical modification of the antibiotic molecule. Objective: The aim of this study was verification of the hypothesis that introduction of bulky substituents at the amino sugar moiety of the antibiotic may result in diminishment of mammalian in vitro toxicity of thus prepared AmB derivatives. Methods: Twenty-eight derivatives of AmB were obtained upon chemical modification of the amino group of mycosamine residue. This set comprised 10 N-succinimidyl-, 4 N-benzyl-, 5 Nthioureidyl- and 9 N-aminoacyl derivatives. Parameters characterizing biological in vitro activity of novel compounds were determined. Results: All the novel compounds demonstrated lower than AmB antifungal in vitro activity but most of them exhibited negligible cytotoxicity against human erythrocytes and three mammalian cell lines. In consequence, the selective toxicity of majority of novel antifungals, reflected by the selective toxicity index (STI = EH50/IC50) was improved in comparison with that of AmB, especially in the case of 5 compounds. The novel AmB derivatives with the highest STI, induced substantial potassium efflux from Candida albicans cells at concentrations slightly lower than IC50s but did not trigger potassium release from human erythrocytes at concentrations lower than 100 μg/mL. Conclusion: Some of the novel AmB derivatives can be considered promising antifungal drug candidates.