The series of a new fluconazole-based conjugates with cell penetrating and antimicrobial peptides

Peptide Fluconazole-Based Conjugates Selected CPP and AMP peptides: CPPs serving as carrier peptides and are considered the fundamental part of an extensively developed concept of a drug delivery system; TP-10 is one of the most promising peptides in this family.These peptides effectively penetrate cell membrane. Modified fragments of bovine lactoferrin (LFcin) and human lactoferrin (HLopt2) are members of the AMP family, peptides that constitute an important segment of the body's natural immunity against microorganisms. P5 and P9 are AMPs, which are designed based on Artisicluthys nobilia interferon-I, inhibit Methicillin-resistant Staphylococcus aureus (MRSA) and show low cytotoxicity.Fluconazole (FLC) is a drug used to treat a number of fungal infections (particularly Candida infections).It inhibits the lanosterol 14demethylase and decreases the level of ergosterol required for the integrity of fungal cell membranes.FLC causes the accumulation of the ergosterol precursors (lanosterol, 4,14-dimethylzymosterol, and 24-methylenedihydrolanosterol) inside the cell, resulting in the altered structure and functioning of the cell membranes [1].Fluconazole was the first triazole antifungal drug introduced in the medicinal practice.In all studied conjugates, glutaric acid served as a linker, forming covalent bonds between hydroxyl group of FLC and N-terminal amino group of the peptide (ester and amide moieties, respectively).