Alterations Produced by Sertaconazole on the Morphology and Ultrastructure of Candida albicans: Sertaconazol‐bedingte Veranderungen der Morphologie und Ultrastruktur von Candida albicans

Abstract

Summary: We studied the changes produced in Candida albicans yeast cells after treatment in vitro with sertaconazole, with light microscopy, transmission and scanning electron microscopy. Four different concentrations were evaluated (10‐‐6 M, 10‐‐5 M, 10‐‐4 M, 10‐‐3 M) and two times of action (12 and 17 h) for each concentration. This new antimycotic agent shows a considerable destructive effect in C. albicans cells. The alterations produced by sertaconazole were already manifested after 12 h at the concentration of 10‐‐6 M and a strong fungicidal activity recorded at 10‐‐4 M. Zusammenfassung: Es wurden die Sertaconazol‐bedingten Veränderungen an der Hefephase von Cadiah albicans in vitro lichtmikroskopisch, raster‐ und transmissionselektronenmikroskopisch bei Einwirkung von vier unterschiedlichen Konzentrationen (10‐‐6, 10‐‐5, 10‐‐3 M) und zwei verschiedenen Einwirkungszeiten (12 und 17 h) untersucht. Dieses neue Antimyzetikum zeigt einen erheblichen Zerstörungseffekt auf C. albicans‐Zellen. Die Veranderungen waren bereits 12 h nach Einwirkung von 10‐‐6 M Sertaconazol manifest. Fungizide Aktivität wurde bei 10‐‐4 M Sertaconazol‐Einwirkung beobachtet.

Successful treatment with sertaconazole of microsporia in a patient infected from an elephant (in Russian only)

“…Его MIC 50 и MIC 90 были равны 0,25 и 0,5 мкг/мл соответственно [12]. Cертаконазол оказывает прямое токсическое влияние на клеточную мембрану грибковых клеток всего через 10 мин после начала воздействия и обеспечивает гибель 90% грибковых клеток в течение 1 ч экспозиции сертаконазола в концентрации 0,008 г/мл [13]. Эффективность сертаконазола доказана как in vitro, так и in vivo.…”

Sertaconazole: an antifungal agent for the topical treatment of superficial candidiasis

“…The inhibition of ergosterol biosynthesis is determined by inhibiting the P450dependent Erg11p enzyme. In this way, the P450-dependent Erg11p enzyme is not able to catalyze the methylation of lanosterol to ergosterol, resulting in a damaged fungal cell membrane without the main bioregulator of fluidity, asymmetry and integrity [16][17][18][19][20]. Sertaconazole interacts with its biosynthetic route, depleting the levels of ergosterol and affecting the integrity of the cell producing lanosterol which damages the cellular architecture, fluidity and membrane permeability [19,20].…”

“…In this way, the P450-dependent Erg11p enzyme is not able to catalyze the methylation of lanosterol to ergosterol, resulting in a damaged fungal cell membrane without the main bioregulator of fluidity, asymmetry and integrity [16][17][18][19][20]. Sertaconazole interacts with its biosynthetic route, depleting the levels of ergosterol and affecting the integrity of the cell producing lanosterol which damages the cellular architecture, fluidity and membrane permeability [19,20]. Interaction between the azole molecule and the iron atom of the hemo group leads to the inactivation of the enzyme 14α-lanosterol demethylase.…”

“…This action could prevent the adhesion of the fungus to the human surfaces, considered an essential step to start the infection [21,22]. Even at lower MICs, sertaconazole is able to produce the inhibition of the hypha development and the accumulation of shorter, less developed and clustered blastoconidia [19,20,22,23].…”

“…This fungicidal effect also depends on the cell growth phase and takes place after 1 h of cell-drug contact at concentrations higher than sertaconazole MIC requiring between 5 and 10 h of contact [21,22,[24][25][26]. The fungicidal activity is achieved at high concentrations of sertaconazole driving to an increased cell permeability and causing intracellular ATP leakage, damage to the cytoskeleton and lysis of cell organules, thus reducing the number of viable cells by up to 90% [2, [19][20][21][22]24,27]. This fungicidal action seems to be higher than those observed in other azoles.…”