Synthesis and in Vitro Antiproliferative Activity of New Phenylaminoisoquinolinequinones against Cancer Cell Lines

Abstract

A variety of phenylaminoisoquinolinequinones were synthesized and tested for their antiproliferative activity against three human-tumor derived cancer cell lines. The new aminoquinones were prepared from 4-methoxycarbonyl-3-methylisoquinoline-5,8-quinone (1) via acid-induced amination and bromination reactions. Remarkable differences in antiproliferative activity were observed depending upon the location and donor capacity of the substituted phenylamino group at the quinone nucleus. The effect of the substituents on the biological activity is discussed in terms of the donor-acceptor interactions which were evaluated through the redox properties of the aminoquinones.

Preparation of Novel Homodimers Derived from Cytotoxic Isoquinolinequinones. A Twin Drug Approach

“…The differences in the regiochemistry of the oxidative amination reaction of quinones 1 and 3 with amine 5 , are in agreement with previous studies on the oxidative amination of isoquinolinequinones with amines. For instance, it was determined that quinone 1 reacts with alkyl- and arylamines in a regiospecific manner to furnish the respective 7-substituted regioisomers [ 9 , 11 ]. In the case of quinone 3 , the amination reactions take place with regioselective preferences to give the 7-substituted regioisomers, as the main products, along with the 6-substituted regioisomers [ 18 ].…”

“…Since many of the currently available anticancer drugs are incapable of differentiating between normal and neoplastic cells, there is a pressing need for new anticancer agents with high potency and less toxicity to noncancerous cells. Among the broad variety of synthetic quinonoid compounds, a group of donor–acceptor members derived from 2-anilino-1,4-naphoquinone and 7-anilinoisoquinoline-5,8-quinone analogues such as compounds A, B and C ( Figure 1 ), have a wide range of remarkable in vitro cytotoxic activity against a variety of cancer cell lines [ 7 , 8 , 9 , 10 , 11 ].…”

Antiproliferative Activity of New 6-Bromine Derivatives of 7-Anilino-1-Arylisoquinolinequinones

“…The reaction proceeded cleanly to give the corresponding bromine compounds 2a-g in good yields (Figure 2). The structures of the new compounds 2a-g were established on the basis of their nuclear magnetic resonance ( 1 H NMR, 13 C NMR) and high resolution mass spectra (HRMS).…”

“…1 H-NMR spectra were recorded on Bruker AM-400 instrument in deuterochloroform (CDCl 3 ). 13 C-NMR spectra were obtained in CDCl 3 at 100 MHz. …”

“…These data indicate that the insertion of nitrogen and halogen atoms in the quinone nucleus moiety have influence on the cytotoxicity of the isoquinoline-5,8-quinone scaffold. Hence, this structural array has stimulated the synthesis of novel aminoisoquinoline-5,8-quinones mainly directed to extend the spectrum of biological activity on cancer cells [9][10][11][12][13][14][15][16].…”