Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Synthesis, biological evaluation and QSAR studies of new thieno[2,3-d]pyrimidin-4(3H)-one derivatives as antimicrobial and antifungal agents
Δημιουργός/Συγγραφέας:	Magoulas, George E Kalopetridou, Lefkothea Ciric, Ana Kritsi, Eftichia Kouka, Paraskevi [EL] Ζουμπουλάκης, Παναγιώτης[EN] Zoumpoulakis, Panagiotis [EL] Χονδρογιάννη, Νίκη[EN] Chondrogianni, Niki Soković, Marina [EL] Προύσης, Κυριάκος[EN] Prousis, Kyriakos [EL] Καλογεροπούλου, Θεοδώρα[EN] Calogeropoulou, Theodora
Εκδότης:	Elsevier
Ημερομηνία:	2021-01
Γλώσσα:	Αγγλικά
ISSN:	00452068
DOI:	10.1016/j.bioorg.2020.104509
Άλλο:	33288321
Περίληψη:	A series of new thieno[2,3-d]pyrimidin-4(3H)-one derivatives were synthesized and evaluated for their activity against four gram-positive and four gram-negative bacterial and eight fungal species. The majority of the compounds exhibited excellent antimicrobial and antifungal activity, being more potent than the control compounds. Compound 22, bearing a m-methoxyphenyl group and an ethylenediamine side chain anchored at C-2 of the thienopyrimidinone core, is the most potent antibacterial compound with broad antimicrobial activity with MIC values in the range of 0.05-0.13 mM, being 6 to 15 fold more potent than the controls, streptomycin and ampicillin. Furthermore, compounds 14 and 15 which bear a p-chlorophenyl and m-methoxyphenyl group, respectively, and share a 2-(2-mercaptoethoxy)ethan-1-ol side chain showed the best antifungal activity, being 10-15 times more potent than ketoconazole or bifonazole with MIC values 0.013-0.026 and 0.027 mM, respectively. Especially in the case of compound 15 the low MIC values were accompanied by excellent MFC values ranging from 0.056 to 0.058 mM. Evaluation of toxicity in vitro on HFL-1 human embryonic primary cells and in vivo in the nematode C. elegans revealed no toxic effects for both compounds 15 and 22 tested at the MIC concentrations. Ligand-based similarity search and molecular docking predicted that the antibacterial activity of analogue 22 is related to inhibition of the topoisomerase II DNA gyrase enzyme and the antifungal activity of compound 15 to CYP51 lanosterol demethylase enzyme. R-Group analysis as a means of computational structure activity relationship tool, highlighted the compounds' crucial pharmacophore features and their impact on the antibacterial and antifungal activity. The presence of a N-methyl piperidine ring fused to the thienopyrimidinone core plays an important role in both activities.
Τίτλος πηγής δημοσίευσης:	Bioorganic chemistry
Τόμος/Κεφάλαιο:	106
Σελίδες:	104509
Θεματική Κατηγορία:	[EL] Μικροβιολογία[EN] Microbiology [EL] Βιοχημεία[EN] Biochemistry [EL] Κυτταρολογία[EN] Cytology [EL] Δομική Βιολογία[EN] Structural Biology [EL] Οργανική χημεία[EN] Organic chemistry [EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry
Λέξεις-Κλειδιά:	Antimicrobial activity Pharma RQSAR Thienopyrimidinones Toxicity studies Anti-Bacterial Agents Antifungal Agents Bacteria Cells, Cultured Dose-Response Relationship, Drug Fungi Humans Microbial Sensitivity Tests Molecular Structure Pyrimidinones Quantitative Structure-Activity Relationship
Κάτοχος πνευματικών δικαιωμάτων:	Copyright © 2020 Elsevier Inc. All rights reserved.
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://www.sciencedirect.com/science/article/abs/pii/S0045206820318071?via%3Dihub
Ηλεκτρονική διεύθυνση περιοδικού (link) :	https://www.sciencedirect.com/journal/bioorganic-chemistry
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο