Some new 3 H -quinazolin-4-one derivatives were synthesised and screened for anticancer, antiphospholipases, antiproteases, and antimetabolic syndrome activities. Compound 15d was more potent in reducing the cell viabilities of HT-29 and SW620 cells lines to 38%, 36.7%, compared to 5-FU which demonstrated cell viabilities of 65.9 and 42.7% respectively. The IC 50 values of 15d were ∼20 µg/ml. Assessment of apoptotic activity revealed that 15d decreased the cell viability by down regulating Bcl2 and BclxL. Moreover, compounds, 8j , 8d / 15a / 15e , 5b, and 8f displayed lowered IC 50 values than oleanolic acid against proinflammatory isoforms of hGV, hG-X, NmPLA 2, and AmPLA 2 . In addition, 8d , 8h , 8j , 15a , 15b , 15e , and 15f showed better anti-α-amylase than quercetin, whereas 8g , 8h , and 8i showed higher anti-α-glucosidase activity than allopurinol. Thus, these compounds can be considered as potential antidiabetic agents. Finally, none of the compounds showed higher antiproteases or xanthine oxidase activities than the used reference drugs.

Colorectal carcinogenesis is a complex process, which is linked to dysregulation of human secretory phospholipases A 2 (hsPLA 2 -G-IIA, hsPLA 2 -G- V , and hsPLA 2 -G- X) , proteases (cathepsin-B, collagenase, thrombin, elastase, and trypsin), carbohydrate hydrolyzing enzymes (α-amylase and α-glucosidase), and free radical generating enzyme (xanthine oxidoreductase (XOR)). Therefore, some new quinazolinones were synthesized and evaluated as inhibitors against this array of enzymes as well as cytotoxic agents on LoVo and HCT-116 cells of colorectal cancer. Compounds 3g , 10 , 8 , 3c , and 1c exhibited promising cytotoxic effects with IC 50 values ranging from 206.07 to 459.79 μM. Nine compounds showed promising enzymatic inhibitory effects, 3b , 3d , 3f , 5 , 1a , and 12 (α-amylase), 8 (thrombin, elastase and trypsin), 10 (hsPLA 2 -G-IIA and hsPLA 2 -G-V), and 3f (α-glucosidase and XOR). Therefore, the most active inhibitors, were subjected to validated molecular docking studies to identify their affinities and binding modes. The expected physicochemical and pharmacokinetic features of the active candidates, 1a , 1c , 3b , 3c , 3d , 3f , 3g , 5 , 8 , 10 , and 12 were predicted using bioavailability radar charts and boiled-egg graphical representations along with the Lipinski rule of five filter. Collectively, these studies showed the significance of derivatives 1c , 3b , 3c , 3d , 8 , 10 , and 12 as lead scaffolds for further optimization to develop enzymes inhibitors and anti-colorectal agents.

CCDC no.: 1459326The asymmetric unit of the title crystal structure is shown in the gure. Tables 1 and 2 contain details on crystal structure and measurement conditions and a list of the atoms including atomic coordinates and displacement parameters. Source of materialTo a stirred solution of 6-methoxy-1-tetralone (5 g, 0.0028 mol) in conc. HCl (28 mL) and glacial acetic acid