Synthesis and in Vitro Cytotoxic Evaluation of Aminoquinones Structurally Related to Marine Isoquinolinequinones

Abstract

The synthesis of 4-methoxycarbonyl-3-methylisoquinolinequinone (1) and a variety of its substitution products with amino-, alkylamino and halogen groups on the quinone nucleus is reported. The series of 6-, 7- and 6,7-subtituted isoquinolinequinones were evaluated in vitro for their cytotoxic activity using the MTT colorimetric method. All the newly synthesized compounds showed moderate to high potency against MRC-5 healthy lung fibroblasts and four human tumor cell lines: AGS gastric adenocarcinoma, SK-MES-1 lung, J82 bladder carcinoma, and HL-60 leukemia cells. Among the series, compounds 4b, 12 and 13 exhibited interesting antitumor activity against human gastric adenocarcinoma, human lung and human bladder carcinoma cancer cells. 7-Amino-6-bromoisoquinoline-5,8-quinone (13) was found to be the most promising active compound against the tested cancer cell lines, with IC50 values in the 0.21−0.49 μM range, lower than the anti-cancer agent etoposide used as reference.

Synthetic approaches and in vitro cytotoxic evaluation of 2-acyl-3-(3,4,5-trimethoxyanilino)-1,4-naphthoquinones

“…1 H NMR spectra were recorded on Bruker Avance-400 instrument and Bruker Ultrashield-300 in deuterochloroform (CDCl 3 ). 13 C NMR spectra were obtained in CDCl 3 at 100 and 75 MHz.…”

“…[5][6][7][8][9][10][11][12][13] The 2-acyl-1,4-benzo-and 1,4-naphthoquinones exhibit remarkable features in terms of their reactivity with nucleophiles due to the fact that the electrophilic centers at the quinone nucleus and acyl substituent are suitably located, thus enabling reactions with compounds such as arylamines [14][15][16] azaenamines 17 enaminones 18,19 and 2-aminobenzothiazoles 20 to give rise to a broad variety of quinonoid compounds such as those depicted in Fig. 1.…”

Quinone‐Fused Pyrazoles through 1,3‐Dipolar Cycloadditions: Synthesis of Tricyclic Scaffolds and in vitro Cytotoxic Activity Evaluation on Glioblastoma Cancer Cells

“…To synthesize as mall library of substituted compounds,w ed ecided to engage three different (hetero)aryl-substituted b-amino nitro-olefins 1a-c and b-enamino esters 3a-c in the above-mentioned isoquinolino-5,8diones formation reaction( Scheme 2, top and middle). [19] For the synthesis of hydrazonoyl chlorides 7 and 8,w eu sed am ethodology already reported by us. [19] For the synthesis of hydrazonoyl chlorides 7 and 8,w eu sed am ethodology already reported by us.…”

“…For the synthesis of isoquinolino-5,8-diones 2 and 4 we soughtt oe mploy ap ublished procedure by Valderrama and colleagues [19] involving ac yclocondensation-oxidation reaction between 2,5-dihydroxybenzaldehyde and electron-poor enamines, promoted by silver oxide. To synthesize as mall library of substituted compounds,w ed ecided to engage three different (hetero)aryl-substituted b-amino nitro-olefins 1a-c and b-enamino esters 3a-c in the above-mentioned isoquinolino-5,8diones formation reaction( Scheme 2, top and middle).…”

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

“…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].…”