Cell Wall Synthesis Inhibitors: Echinocandins and Nikkomycins

Abstract

Abstract Ever since the discovery that penicillin inhibits bacterial cell wall synthesis, developing equivalent agents to target the fungal cell wall has been a focus in antifungal drug development. Because the cell wall is essential to the vitality of fungal organisms and because its components are absent in the mammalian host, the fungal cell wall represents an ideal target for antifungal compounds. With considerable variation among different species, the gross macromolecular components of the cell wall of most fungi include chitin, alpha- or beta-linked glucans and a variety of mannoproteins. The dynamics of the fungal cell wall are closely coordinated with cell growth and cell division, and its predominant function is to control the internal turgor pressure of the cell. Disruption of the cell wall structure leads to osmotic instability, and may ultimately result in the lysis of the fungal cell. Systemic antifungal agents directed against or involving the major constituents of the fungal cell wall include the new class of echinocandin lipopeptides and the nucleoside-peptide antibiotic nikkomycin Z.