Reactivity and Anticancer Assessment of 4-Hydroxyquinoline Derivatives

Abstract

Ethyl 4-hydroxy-7-(trifluoromethyl)quinoline-3-carboxylate (1) exhibits a moderate cytotoxic activity against the MCF-7 mammary gland cancer cell line and HePG2 hepatocellular carcinoma cell line and a weak activity against the HCT-116 human colorectal carcinoma cell line. In order to enhance the cytotoxic activity of this compound, it was modified by changing the side-chain substituent and/or forming a new heterocyclic ring fused to the pyridine ring. Heating compound 1 with chloroacetyl chloride gave a mixture of two isomeric O-acylation products ethyl 4-(2-chloroacetoxy)-7-(trifluoromethyl)-quinoline-3-carboxylate and 3-chloro-8-(trifluoromethyl)-2H-pyrano[3,2-c]quinoline-2,4(3H)-dione, whereas the reaction with acetyl chloride in NaOH formed an N-acylation product 1-acetyl-4-oxo-7-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylic acid. The reactions of compound 1 with urea, thiourea, hydrazine hydrate, hydroxylamine, o-phenylenediamine, phenyl isothiocyanate, and ethyl acetoacetate yielded the corresponding condensation products 1-[4-oxo-7-(trifluoromethyl)-3,4-dihydroquinoline-3-carbonyl)]urea, 1-[4-oxo-7-(trifluoromethyl)-3,4-dihydroquinoline-3-carbonyl)]thiourea, 7-(trifluoromethyl)-1,2-dihydropyrazolo[4,3-c]quinolin-3-one, 7-(trifluoromethyl)isoxazolo[4,5-c]quinolin-3(2H)-one, 3-(trifluoromethyl)-13H-benzo[2,3][1,4]diazepino[6,5-c]quinolin-7-ol, 3-phenyl-2-thioxo-8-(trifluoromethyl)-2,3-dihydro-4H-[1,3]oxazino[5,6-c]quinolin-4-one and ethyl 8-(trifluoromethyl)-2-methyl-4-oxo-4H-pyrano[3,2-c]quinolone 3-carboxylate, respectively. The structures of the synthesized compounds were confirmed by elemental analysis and spectral data.