25628-84-6Relevant academic research and scientific papers
Design, synthesis, molecular docking, and some metabolic enzyme?inhibition properties of novel quinazolinone derivatives
Tokal?, Feyzi S.,Taslimi, Parham,Demircio?lu, ?brahim H.,Karaman, Muhammet,Gültekin, Mehmet S.,?endil, K?v?lc?m,Gül?in, ?lhami
, (2021)
3-Amino-2-ethylquinazolin-4(3H)-one (3) was synthesized in two steps from the reaction of amide (2), which was obtained from the treatment of methyl anthranilate (1) with propionyl chloride, with hydrazine. From the reaction of 3-amino-2-ethylquinazolin-4(3H)-one (3) with various aromatic aldehydes, novel benzylidenaminoquinazolin-4(3H)-one (3a–n) derivatives were synthesized. The structures of the novel molecules were characterized using infrared spectroscopy, nuclear magnetic resonance spectroscopy (1H-NMR and 13C-NMR), and high-resolution mass spectroscopy. The novel compounds were tested against some metabolic enzymes, including α-glucosidase (α-Glu), acetylcholinesterase (AChE), and human carbonic anhydrases I and II (hCA I and II). The novel compounds showed Ki values in the range of 244–988 nM for hCA I, 194–900 nM for hCA II, 30–156 nM for AChE, and 215–625 nM for α-Glu. The binding affinities of the most active compounds were calculated as ?7.636, ?6.972, ?10.080, and ?8.486 kcal/mol for hCA I, hCA II, AChE, and α-Glu enzymes, respectively. The aromatic ring of the quinazoline moiety plays a critical role in the inhibition of the enzymes.
Synthesis, biological evaluation, and in silico study of novel library sulfonates containing quinazolin-4(3H)-one derivatives as potential aldose reductase inhibitors
Demir, Yeliz,Kalay, Erbay,?endil, K?v?lc?m,Beydemir, ?ükrü,Demircio?lu, ?brahim Hakk?,Türke?, Cüneyt,Tokal?, Feyzi Sinan
, (2021/10/01)
A series of novel sulfonates containing quinazolin-4(3H)-one ring derivatives was designed to inhibit aldose reductase (ALR2, EC 1.1.1.21). Novel quinazolinone derivatives (1–21) were synthesized from the reaction of sulfonated aldehydes with 3-amino-2-alkylquinazolin-4(3H)-ones in glacial acetic acid with good yields (85%–94%). The structures of the novel molecules were characterized using IR, 1H-NMR, 13C-NMR, and HRMS. All the novel quinazolinones (1–21) demonstrated nanomolar levels of inhibitory activity against ALR2 (KIs are in the range of 101.50–2066.00 nM). Besides, 4-[(2-isopropyl-4-oxoquinazolin-3[4H]-ylimino)methyl]phenyl benzenesulfonate (15) showed higher inhibitor activity inhibited ALR2 up to 7.7-fold compared to epalrestat, a standard inhibitor. Binding interactions between ALR2 and quinazolinones have been investigated using Schr?dinger Small-Molecule Drug Discovery Suite 2021–1, reported possible inhibitor-ALR2 interactions. Both in vitro and in silico study results suggest that these quinazolin-4(3H)-one ring derivatives (1–21) require further molecular modification to improve their drug nominee potency as an ALR2 inhibitor.
Fragment-based lead discovery: Screening and optimizing fragments for thermolysin inhibition
Englert, Lisa,Silber, Katrin,Steuber, Holger,Brass, Sascha,Over, Bjoern,Gerber, Hans-Dieter,Heine, Andreas,Diederich, Wibke E.,Klebe, Gerhard
experimental part, p. 930 - 940 (2011/02/24)
Fragment-based drug discovery has gained a foothold in today's lead identification processes. We present the application of in silico fragment-based screening for the discovery of novel lead compounds for the metalloendoproteinase thermolysin. We have chosen thermolysin to validate our screening approach as it is a well-studied enzyme and serves as a model system for other proteases. A protein-targeted virtual library was designed and screening was carried out using the program AutoDock. Two fragment hits could be identified. For one of them, the crystal structure in complex with thermolysin is presented. This compound was selected for structure-based optimization of binding affinity and improvement of ligand efficiency, while concomitantly keeping the fragment-like properties of the initial hit. Redesigning the zinc coordination group revealed a novel class of fragments possessing Ki values as low as 128 μm, thus they provide a good starting point for further hit evolution in a tailored lead design.
