Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Novel Multi-Target Agents Based on the Privileged Structure of 4-Hydroxy-2-quinolinone
Δημιουργός/Συγγραφέας:	Kostopoulou, Ioanna Tzani, Andromachi Chronaki, Konstantina [EL] Προύσης, Κυριάκος[EN] Prousis, Kyriakos Pontiki, Eleni Hadjiplavlou-Litina, Dimitra Detsi, Anastasia
Ημερομηνία:	2023-12-28
Γλώσσα:	Αγγλικά
ISSN:	1420-3049
DOI:	10.3390/molecules29010190
Άλλο:	38202773
Περίληψη:	In this work, the privileged scaffold of 4-hydroxy-2quinolinone is investigated through the synthesis of carboxamides and hybrid derivatives, as well as through their bioactivity evaluation, focusing on the ability of the molecules to inhibit the soybean LOX, as an indication of their anti-inflammatory activity. Twenty-one quinolinone carboxamides, seven novel hybrid compounds consisting of the quinolinone moiety and selected cinnamic or benzoic acid derivatives, as well as three reverse amides are synthesized and classified as multi-target agents according to their LOX inhibitory and antioxidant activity. Among all the synthesized analogues, quinolinone-carboxamide compounds 3h and 3s, which are introduced for the first time in the literature, exhibited the best LOX inhibitory activity (IC50 = 10 μM). Furthermore, carboxamide 3g and quinolinone hybrid with acetylated ferulic acid 11e emerged as multi-target agents, revealing combined antioxidant and LOX inhibitory activity (3g: IC50 = 27.5 μM for LOX inhibition, 100% inhibition of lipid peroxidation, 67.7% ability to scavenge hydroxyl radicals and 72.4% in the ABTS radical cation decolorization assay; 11e: IC50 = 52 μM for LOX inhibition and 97% inhibition of lipid peroxidation). The in silico docking results revealed that the synthetic carboxamide analogues 3h and 3s and NDGA (the reference compound) bind at the same alternative binding site in a similar binding mode.
Τίτλος πηγής δημοσίευσης:	Molecules (Basel, Switzerland)
Τόμος/Κεφάλαιο:	29
Τεύχος:	1
Σελίδες:	190
Θεματική Κατηγορία:	[EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry [EL] Χημική Βιολογία[EN] Chemical Biology [EL] Οργανική χημεία[EN] Organic chemistry [EL] Δομική Βιολογία[EN] Structural Biology
Λέξεις-Κλειδιά:	4-hydroxy-2-quinolinone Carboxamides Antioxidant activity Lipoxygenase inhibition Structure–activity relationships Molecular docking
Κάτοχος πνευματικών δικαιωμάτων:	© 2023 by the authors. Licensee MDPI, Basel, Switzerland.
Όροι και προϋποθέσεις δικαιωμάτων:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://doi.org/10.3390/molecules29010190
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο