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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-2ethylquinazolin-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 ( 1 H-NMR and 13 C-NMR), and highresolution 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. K E Y W O R D S3-aminoquinazolin-4(3H)-one, enzyme inhibition, metabolic enzymes, molecular docking, Schiff bases | INTRODUCTIONQuinazolines and quinazolinone derivatives are molecules that represent an important class of heterocyclic compounds. This class of compounds that are known to be natural and synthetic derivatives has attracted the attention of many scientists due to their biological activities and many molecules belonging to this class of compounds have been synthesized in the past 30 years. Many studies concerning anticancer, [1][2][3][4] antitumor, [5,6] antimicrobial, [7][8][9] anti-inflammatory, [10] antifungal, [11] anticonvulsant, [12,13] and anti-HIV [14] properties of quinazoline and quinazolinone derivatives have been reported.Carbonic anhydrases (CAs) are metalloenzymes widespread in nature, being encoded by at least eight genetic classes, which have been identified in organisms. [15,16] By catalyzing a crucial physiologic reaction, by which carbon dioxide is hydrated with the formation of a weak base (bicarbonate) and a strong acid (hydronium ions), these enzymes are involved in plenty of physiologic mechanisms, starting with pH regulation and ending with metabolism. [17,18] Thus, CAs and their inhibitors are drugs having pharmacological applications in many fields. For example, CA II isoenzyme is the most physiologically relevant isoform and is implicated in diseases like glaucoma (such as CA XII), cerebral edema, and epilepsy. [19][20][21]

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Plants use light for photosynthesis and for various signaling purposes. The UV wavelengths in sunlight also introduce DNA damage in the form of cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts [(6-4)PPs] that must be repaired for the survival of the plant. Genome sequencing has revealed the presence of genes for both CPD and (6-4)PP photolyases, as well as genes for nucleotide excision repair in plants, such as Arabidopsis and rice. Plant photolyases have been purified, characterized, and have been shown to play an important role in plant survival. In contrast, even though nucleotide excision repair gene homologs have been found in plants, the mechanism of nucleotide excision repair has not been investigated. Here we used the in vivo excision repair assay developed in our laboratory to demonstrate that Arabidopsis removes CPDs and (6-4)PPs by a dual-incision mechanism that is essentially identical to the mechanism of dual incisions in humans and other eukaryotes, in which oligonucleotides with a mean length of 26-27 nucleotides are removed by incising ∼20 phosphodiester bonds 5′ and 5 phosphodiester bonds 3′ to the photoproduct.lants and other organisms that depend on photosynthesis are, by necessity, exposed to more sunlight than other organisms that are chemotrophs or heterotrophs. Hence, plants are expected to receive more exposure to UV wavelengths of light than other organisms. The genotoxic effects of UV are somewhat mitigated by the reflection of UV by the waxy leaf surface and absorbance of UV by the intracellular pigments that are present at high concentration in plant cells, including carotenoids and flavonoids. Nevertheless, plants still receive considerable amounts of DNA-damaging UV radiation and therefore must have the means to cope with the damage to ensure their survival. Indeed, DNA sequencing has revealed that plant genomes contain genes that are homologous to the genes of all major DNA repair pathways, including photoreactivation, nucleotide excision repair, base excision repair, and recombination/double-strand break repair (1-6).However, biochemical studies of these DNA repair mechanisms have been limited. Of significance, Arabidopsis photolyases have been expressed in heterologous systems, purified, and characterized (7-9). Similarly, some of the enzymes of the base excision repair and recombination/double-strand break repair systems have been studied. In contrast, there have been no mechanistic studies on plant nucleotide excision repair, although it is known that plants can remove cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts [(6-4)PPs] in a photolyase-independent manner (6, 10, 11), presumably by nucleotide excision repair. Here, we have used an Arabidopsis cell line and the in vivo excision assay recently developed in our laboratory (12)(13)(14) to demonstrate that Arabidopsis removes these photoproducts by dual incisions in a manner that is virtually identical to human nucleotide excision repair. ResultsNucleotide Ex...