Synthesis and Characterization of New-2,3-Disubstituted Quinazolinone Derivatives as Antibacterial Agents

Abstract

In this work, some new 2,3-disubsituted quinazolinone derivatives were synthesized. The reaction of substituted anthranilic acid with 3-chlorophenylisothiocyanate gave the compounds [3-(3-chlorophenyl)-2-mercaptoquinazoline-4(3H)-one] (1a,b). compounds (1a,b) where treated with chloroethylacetate in presence of potassium carbonate gave the compounds [-4-oxo-3, 4-dihydroquinazoline-2-yl)thio)acetate] (2a,b). Reaction with hydrazine hydrate afforded the acetohydrazides [-4-oxo-3,4-dihydroquinazoline-2-yl) thio) acetohydrazide](3a,b). The acetoohydrazides (3a,b) were treated with aromatic aldehydes to give the Schiff's bases [-Nˉ-(3nitrobenzylidene)acetohydrazide] (5a,b). Treatment of derivatives (1a,b) with hydrazine hydrate afforded the hydrazine derivatives [-2-hydrazinylquinazoilne-4(3H)-one] (4a,b) which also used in synthesizing Schiff's bases [(E)(2-(3-nitrobenzyllidene)hydrazinyl)] (6a,b). Alkyl halide was treated with compounds (1a,b) in presence acetone to give of [-2-(methylthio)quinazoline-4(3H)-one] (7a,b), and with arylhalide in DMF gave the compounds [-2-((4-nitrophenyl)thio)quinazoline-4(3H)-one)] (8a,b). The structures of all prepared compounds have been elucidated using FTIR, 1 HNMR, and MASS spectroscopy. The antibacterial activity was evaluated for (1,5,6,7)a-b derivatives.

Synthesis and Cytotoxic Activity against K562 and MCF7 Cell Lines of SomeN-(5-Arylidene-4-oxo-2-thioxothiazolidin-3-yl)-2-((4-oxo-3-phenyl-3,4-dihydroquinazoline-2-yl)thio)acetamide Compounds

“…2-Mercapto-3-phenylquinazolin-4-one (2), ethyl 2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetate (3), and 2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetohydrazide (4) were prepared according to reported methods [1,3,7,14,15,18]. e similarity in both melting points and spectral characteristics of these compounds with the ones of the corresponding compounds in literature confirmed their formation.…”

“…Hz, Ar-H), and 7.29 (2H, d, 3 J � 7.5 Hz, Ar-H) (see S1a and S1b from Supporting Information). (3). An equimolar mixture of 2-mercapto-3phenylquinazolin-4-one (2) (5.08 g, 20 mmol) and anhydrous potassium carbonate (2.76 g, 20 mmol) in dry DMF (30 mL) was stirred for 30 minutes, and then, ethyl chloroacetate (2.45 g, 20 mmol) was added.…”

“…Yield: 65.0%; mp: 106-107°C (lit. [45]: 105-107°C); IR (], cm − 1 ): 3059 (C-H aromatic), 2976, 2906 (C-H aliphatic), 1732 (C�O ester), 1680 (C�O ketone), 1607, 1598, and 1468 (C�N, C�C aromatic); 1 H-NMR (δ, ppm): 8.09 (1H, d, 3 J � 8.0 Hz, Ar-H), 7.84 (1H, d, 3 J � 7.5 Hz, Ar-H), 7.61-7.48 (7H, m, Ar-H), 4.15 (2H, q, 3 J � 7.0 Hz, -CH 2 CH 3 ), 3.99 (2H, s, -SCH 2 -), and 1.23 (3H, t, 3 J � 7.0 Hz, CH 3 ) (see S2a and S2b from Supporting Information). (4).…”

“…Quinazolinones were considered to be a scaffold with potential biological activities. Besides possessing a variety of biological effects including antimicrobial [1][2][3][4][5][6], anticonvulsant [7,8], and antihistamine [9,10] activities, compounds containing quinazolin-4-one nucleus also showed promising anticancer potency [11][12][13][14][15][16][17][18][19][20]. Along with that, 5-arylidene-2thioxothiazolidine-4-one compounds are an important class of compounds with a wide range of pharmaceutical properties.…”

“…-CH � ), 8.10 (1H, d,3 J � 8.0, Ar-H), 7.96-7.87 (2H, m, Ar-H), 7.80-7.77 (3H, m, Ar-H), 7.64-7.58 (3H, m, Ar-H), 7.52-7.49 (3H, m, Ar-H), and 4.18 (2H, m, -CH 2 -);13 C-NMR (δ, ppm) 190.7 (C�S), 166.3, 162.8, 161.2 (C�O), 156.5, 148.3, 147.6, 136.2, 135.3, 132.4, 132.2, 130.6, 130.1, 130.0, 129.9, 128.9, 127.0, 126.95, 126.6, 126.2, 124., 163.0, 161.2 (C�O), 156.5, 147.6, 146.9, 136.2, 135.9, 135.7, 135.3, 130.8, 130.5, 130.1, 129.9, 129.5, 128.8, 127.0, 126.9, 126.6, 123.5, 120.7, and 120.0 (C Ar and C ankene ), 34.5 (-CH 2 -); HR-ESI-MS m/z 557.0791 (M + H) + calcd. for (C 28 H 21 N 4 O 3 S 3 ) 557.0770 (see S19a-S19c from Supporting Information).…”