Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Novel hit compounds as putative antifungals: The Case of Aspergillus fumigatus
Δημιουργός/Συγγραφέας:	Kritsi E. Matsoukas M.-T. Potamitis C. Detsi A. Ivanov M. Sokovic M. [EL] Ζουμπουλάκης, Παναγιώτης[EN] Zoumpoulakis, Panagiotis
Εκδότης:	MDPI AG
Ημερομηνία:	2019
Γλώσσα:	Αγγλικά
ISSN:	1420-3049
DOI:	10.3390/molecules24213853
Άλλο:	PubMed ID: 31731542
Περίληψη:	The prevalence of invasive fungal infections has been dramatically increased as the size of the immunocompromised population worldwide has grown. Aspergillus fumigatus is characterized as one of the most widespread and ubiquitous fungal pathogens. Among antifungal drugs, azoles have been the most widely used category for the treatment of fungal infections. However, increasingly, azole-resistant strains constitute a major problem to be faced. Towards this direction, our study focused on the identification of compounds bearing novel structural motifs which may evolve as a new class of antifungals. To fulfil this scope, a combination of in silico techniques and in vitro assays were implemented. Specifically, a ligand-based pharmacophore model was created and served as a 3D search query to screen the ZINC chemical database. Additionally, molecular docking and molecular dynamics simulations were used to improve the reliability and accuracy of virtual screening results. In total, eight compounds, bearing completely different chemical scaffolds from the commercially available azoles, were proposed and their antifungal activity was evaluated using in vitro assays. Results indicated that all tested compounds exhibit antifungal activity, especially compounds 1, 2, and 4, which presented the most promising minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values and, therefore, could be subjected to further hit to lead optimization.
Τίτλος πηγής δημοσίευσης:	Molecules
Τόμος/Κεφάλαιο:	24
Τεύχος:	21
Θεματική Κατηγορία:	[EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry [EL] Βιοχημεία[EN] Biochemistry
Λέξεις-Κλειδιά:	Antifungal activity Aspergillus fumigatus MFC MIC Molecular docking Molecular dynamics simulations Pharmacophore model Virtual screening
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2019 by the authors.
Όροι και προϋποθέσεις δικαιωμάτων:	All Open Access, Gold, Green
Σημειώσεις:	Grant number 173032; Ministarstvo Prosvete, Nauke i TehnoloÅ¡kog Razvoja, MPNTR.
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο