Synthesis and screening of some new fluorinated quinazolinone-sulphonamide hybrids as anticancer agents

The aim of the present research was to synthesise several novel fluorinated quinazoline-sulphonamide derivatives and to evaluate their in vitro cytotoxic activity. Eight compounds were synthesised. The compounds' anticancer activities were determined through the [3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyltetrazolium bromide] [MTT] assay using a three-cell-line panel consisting of National Cancer Institute [NCI] lung cancer cells, Michigan Cancer Foundation-7 [MCF-7] breast cancer cells, and Human Embryonic Kidney-293 [HEK-293] normal kidney cell. The values of C log P correlations were determined to interpret the results. One compound exhibited significant anticancer activity with low toxicity compared with the methotrexate as the reference drug. The biological screening showed good to moderate anticancer activity for the title compounds compared with the reference drug. The reference drug exhibited an IC[50] value of 2.4 micro M, whereas compound 9, which was identified as the most active compound, exhibited an IC[50] value of 2.51 micro M on the NCI cell line. The other compounds showed IC[50] values that ranged from 2.89 to 46.34 micro M on the three cell lines. The newly synthesized compounds had lower toxicity on the normal cell line than did methotrexate. The newly synthesized compounds may provide a valuable template for future design and optimization to produce analogues that act as more active anticancer agents

New fluorinated quinazolinone derivatives as anticonvulsant agents

The aim of the present work was to synthesize some novel fluorinated quinazolinones and to evaluate them for anticonvulsant activity and neurotoxicity. Eight compounds were synthesized. Their anticonvulsant activity was evaluated from maximal electroshock-induced seizures in eight groups of six Swiss mice given the test compounds [100 mg/kg intraperitoneally], one control group given 10% DMSO [10 ml/kg] and one given the reference compound phenytoin [100 mg/kg]. Neurotoxicity was evaluated by the rotarod test in eight groups of four Swiss mice given the test compounds [100 mg/kg], one given saline [10 ml/kg] and one given phenytoin [100 mg/kg]. The structure-activity relations of the compounds and C log P correlations were determined to explain the results. Four compounds showed significant anticonvulsant activity with low neurotoxicity when compared with the reference drug. The newly designed compounds could be useful templates for the design and optimization of more active analogues as anticonvulsant agents with low neurotoxicity