Synthesis and biochemical evaluation of nucleosides of naphthoquinone heterocycles

Abstract

The synthesis, characterization, and biochemical evaluation of 1-beta-D-ribofuranosylnaphtho[2,3-d]imidazole-4,9-dione (3), 2-beta-D-ribofuranosylnaphtho[2,3-d]pyrazole-4,9-dione (6), and 2-beta-D-ribofuranosylnaphthol[2,3-d]triazole-4,9-dione (9) are reported. These quinone nucleosides and the corresponding quinone heterocycles were tested as inhibitors of purine nucleotide biosynthesis in Ehrlich ascites cells. The nucleosides 3 and 9 and naphtho[2,3-d]imidazole-4,9-dione were effective inhibitors of hypoxanthine phosphoribosyltransferase.

Synthesis and Cytotoxicity of 1,2-Disubstituted Naphth[2,3-d]imidazole-4,9-diones and Related Compounds

“…Evaluation of the cytotoxicity of these 1-substituted-2-methylnaphth [2,3-d]imidazole-4,9-dione derivatives (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) showed that the N-ethyl analog (5) displays strong cytotoxicity. Therefore, we prepared a series of 1-ethyl-2-substituted-naphth[2,3-d]imidazole-4,9-diones (22-28) where the N-1 substituent was fixed as chloride and 1 to react under these conditions has been previously reported by Hoover.…”

“…The quinone moiety is involved in a wide variety of biochemical processes including electron transport and oxidative phosphorylation. Biological activities that have been reported for quinones and quinone derivatives include enzyme inhibition and antibacterial, antifungal, and anticancer activities. , Numerous structurally diverse quinone derivatives have been synthesized and investigated; one class of such compounds is the heterocyclic quinones, including imidazole derivatives of 1,4-naphthoquinones. , Naphth[2,3- d ]imidazole-4,9-dione and its 1-β- d -ribofuranosyl derivative were prepared in a study of naphthoquinone heterocycles and were found to be effective inhibitors of hypoxanthine phosphoribosyltransferase, which is involved in an initial step in purine nucleotide biosynthesis. In addition, the naphthoquinone psychorubrin was isolated as a cytotoxic natural product from Psychotria rubra ( Chiou Chie Mu ) (Rubiaceae) by this laboratory.…”

“…5,6 Numerous structurally diverse quinone derivatives have been synthesized and investigated; one class of such compounds is the heterocyclic quinones, including imidazole derivatives of 1,4-naphthoquinones. 7,8 Naphth[2,3-d]imidazole-4,9-dione 9 and its 1-β-D-ribofuranosyl derivative 10 were prepared in a study of naphthoquinone heterocycles and were found to be effective inhibitors of hypoxanthine phosphoribosyltransferase, 10 which is involved in an initial step in purine nucleotide biosynthesis. In addition, the naphthoquinone psychorubrin was isolated as a cytotoxic natural product from Psychotria rubra (Chiou Chie Mu) (Rubiaceae) by this laboratory.…”

Synthesis of a New Diels-Alder Quinone Adduct and Its Use in Preparing Thiazolo- and Oxazoloquinolines

“…[1][2][3] Thus, among quinones, naphthoquinones have been found to possess good fungicidal 4,5 as well as antimalarial activities. 6 On the other hand, quinones fused to oxazole or thiazole nuclei have been endowed with good bactericidal activity.…”

Synthesis of heterocyclic nitrogen derivatives from aryl‐1,4‐benzoquinones

“…Owing to the importance of quinones which posses a wide spread application in various fields including use as fungicides [1][2][3], antibacterial [4][5][6], antimalarial [7] and as antitumoral [8], we decided to synthesize some new heterocyclic quinones starting with aryl-1,4-benzoquinones (1) [9] hoping that such compounds would have certain required biological effects or other industrial applications.…”