Design, synthesis, molecular docking, and some metabolic enzyme inhibition properties of novel quinazolinone derivatives. Issue 5 (4th February 2021)

• Record Type: Journal Article
• Authors: Tokalı, Feyzi S.; Taslimi, Parham; Demircioğlu, İbrahim H.; Karaman, Muhammet; Gültekin, Mehmet S.; Şendil, Kıvılcım; Gülçin, İlhami
• Is Part Of: Archiv der Pharmazie. Volume 354:Issue 5(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-02-04
• Subjects: 3‐aminoquinazolin‐4(3H)‐one -- enzyme inhibition -- metabolic enzymes -- molecular docking -- Schiff bases; Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.202000455
• Languages: English
• ISSNs: 0365-6233

Abstract

Abstract: 3‐Amino‐2‐ethylquinazolin‐4(3 H )‐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(3 H )‐one (3 ) with various aromatic aldehydes, novel benzylidenaminoquinazolin‐4(3 H )‐one (3a–n ) derivatives were synthesized. The structures of the novel molecules were characterized using infrared spectroscopy, nuclear magnetic resonance spectroscopy ( 1 H‐NMR and 13 C‐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 K i 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. Abstract : Novel benzylidenaminoquinazolin‐4(3 H )‐one (3a –n ) derivatives were synthesized and tested against some metabolic enzymes, including α‐glucosidase, acetylcholinesterase, and human carbonic anhydrases I and II. The aromatic ring of the quinazoline moiety plays a critical role in the inhibition of the enzymes.