ChemInform Abstract: HETEROCYCLIC QUINONES. VI: SYNTHESIS AND ANTITUMORAL EFFECTS OF 5,10‐BENZO(G)QUINOXALINEDIONES AND AZA‐ANALOGS

Abstract

Durch Kondensation der Diaminochinone (I), (IV) bzw. (VI) mit den Dionen (II) werden die Benzochinoxalindione (III) sowie ihre Azaderivate (V) und (VII) erhalten.

Aminonaphthoquinones in heterocyclization

“…Condensation of compound 9 with 1,4‐dibromobutane‐2,3‐dione led to 2,3‐bis(bromo‐methyl)‐benzo[ g ]quinoxaline‐5,10‐dione [36], which was converted to compound 38 by classical chlorination using lithium chloride as illustrated in Scheme [36].…”

“…Reaction of compound 9 with α‐dicarbonyl compounds afford 2,3‐disubstituted benzoquinoxaline‐5,10‐diones 39 as shown in Scheme [36].…”

Correlation between Cytotoxic Activities and Reduction Potentials of Heterocyclic Quinones

“…Several recent publications have highlighted the anti-tumor activity of kigelinone (2-(1-hydroxyethyl)-5(or 8)-hydroxynaphtho[2,3- b ]furan-4,9-dione), a furanonaphthoquinone molecule isolated from Tabebuia cassinoide s [ 5 ]. Heterocyclic quinones containing nitrogen atoms possess excellent anti-tumor [ 6 , 7 ] and other biologic activities [ 8 , 9 ]. Previously, we reported the in vitro anti-tumor promoting activity of heterocyclic quinines, as evidenced by inhibitory effects on 12- O -tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) activation in Raji cells [ 10 , 11 ].…”

Synthesis of original benzo[g]quinoxaline‐5,10‐diones by bis‐SRN1 methodology

“…Another structural requirement for the antitumor activity is the p-quinone moiety in the nonheterocyclic ring, whereas o-quinone gave decreased activity [6]. The electron-withdrawing groups at the 6 and 7 positions of quinolinediones also contributed to the activity [7], Giorgi-Renault prepared benzoquinoxalinediones and pyridoquinoxalinediones, which are quinoxalinediones fused with benzene or pyridine, and examined their cytotoxic properties [8].In continuation to our studies directed toward the synthesis of new nitroheterocyclic or quinonic bioreductible alkylating agents [9] using single electron transfer reactions, we have investigated the reactivity of 2,3-bis-( c h l o r o m e t h y l ) b e n z o [g]quinoxaline-5,10-dione (5) with various aliphatic or cyclic nitronate anions, malonate and S-centered anions in order to prepare original benzo[g]-quinoxaline-5,10-dione derivatives. …”

“…Thus, 1 was first converted into the corresponding diazido derivative 2 using NaN 3 [10], followed by a reduction with Na 2 S 2 O 4 to form 2,3-diamino-1,4-naphthoquinone (3) [11]. The condensation of 3 with 1,4-dibromobutan-2,3-dione led to 2,3-bis(bromomethyl)benzo[g]-quinoxaline-5,10-dione (4) [8,12] which was converted into 5 by classical chlorination using lithium chloride (Scheme 1). The reaction of 2,3-bis(chloromethyl)benzo-…”