Synthesis and cytotoxic evaluation of some derivatives of triazole-quinazolinone hybrids

Abstract

Triazoles and quinazolinones are important heterocyclic structures with diverse biological properties including cytotoxic, antibacterial, antifungal and anticonvulsant activities. Due to valuable cytotoxic effects of both triazole and quinazoline derivatives, in this study a series of quinazolinone-triazole hybrids were synthesized in a multiple-step reaction procedure. 3-Amino-quinazolinone derivatives were treated with chloroacetyl chloride in the presence of dichloromethane/triethylamine to afford 2-chloro -N-(4-oxo-2- quinazolin3 (3H)-yl) acetamide derivatives. The reaction of resultants with 4-mehyl-4-H-1, 2, 4-triazole-3- thiol in dry acetone and potassium carbonate led to the formation of final products. Synthesized compounds were evaluated for their cytotoxic effects against MCF-7 and Hela cell lines using MTT colorimetric assay. Amongst tested compounds, 6a showed the highest cytotoxic activity against MCF7 cell line at all tested concentrations while compounds 6b and 6c indicated mild cytotoxic effects against Hela cell line at highest tested concentration reducing cell viability about 40%. The IC50 values of tested compounds revealed that the MCF-7 is more susceptible to the compound 6a.

Synthesis and cytotoxic evaluation of some quinazolinone- 5-(4-chlorophenyl) 1, 3, 4-oxadiazole conjugates

“…Treatment of 3-amino quinazolinone with chloro acetylchloride in the presence of dichloromethane/triethylamine afforded 2-chloro -N-(4-oxo-2-quinazolin3 (3H)-yl) acetamide derivatives ( 5a-5c ). Final compounds ( 6a-6c ) obtained through the nucleophilic displacement of the chloride with thiol of 5-(4-chlorophenyl) 1, 3, 4- oxadiazole-2-thiol in dry acetone and potassium carbonate (Scheme 1) (2122).…”

“…A mixture of related benzoxazone 3a-3c (0.01 mol) and hydrazine hydrate (0.02 mol) in ethanol was refluxed for 3 h. After the reaction was completed, the mixture was cooled and the separated solid was collected by filtration and recrystallized from ethanol or isopropanol (2122).…”

“…Then the reaction mixture was poured into ice water and extracted with dichloromethane and ethyl acetate. The extracted ethyl acetate was washed with sodium bicarbonate solution (3%) and dried over anhydrous magnesium sulfate, which upon evaporation afforded the products 5a-5c (2122).…”

“…Title compounds 6a-6c were synthesized by refluxing 2-chloro -N-(4-oxo-2-quinazolin3 (3H)-yl) acetamide derivatives 5a-5c (0.01 mol) with 5-(4-chlorophenyl) 1, 3, 4-oxadazole-2- thiol in dry acetone (20 mL) and anhydrous potassium carbonate (0.01 mmol) for 6 h. The reaction mixture was filtered while hot. The organic solution was concentrated and purified by preparative TLC (2122).…”

Recent advances in the pharmacological diversification of quinazoline/quinazolinone hybrids

“…As triazole was found to increase the existing activity of many bioactive scaffolds, 4 Hassanzadeh et al have designed hybrids with the structural features of triazole and quinazolinone. 51 These triazole and quinazolinone scaffolds were linked through a 2-thioacetamido linkage and synthesized via the substitution reaction of 2-chloro-N-(4-oxo-2-quinazolin3(3H)-yl)acetamide derivatives with 4-methyl-4-H-1,2,4-triazole-3-thiol. These synthesized hybrids were tested against MCF-7 and HeLa cell lines and MCF-7 cell line was found to be susceptible to compound 31 with an IC 50 of 38.38 mM (Scheme 11).…”