Comparative study on biological activities of heterocyclic quinones and streptonigrin.

Abstract

Thirteen heterocyclic quinones (5 quinoline quinones, 7 isoquinoline quinones, 1 indole quinone) were tested for their effects on avian myeloblastosis virus reverse transcriptase, growth of murine lymphoblastoma L5178Ycells, respiration of rat liver mitochondria and oxidation of NADH by Clostridium kluyveri diaphorase in comparison with those of streptonigrin, in which the quinoline quinone moiety is considered to play a crucial role.Most of the quinoline quinones and isoquinoline quinones inhibited reverse transcriptase to the same extent as streptonigrin with the ID50 values ranging between 1 and 5^g/ml, whereas the ID50 value of the indole quinone derivative, 4,7-dihydro-2,3-dimethylindole-4,7-dione, was 80^g/ml. The cytotoxicities of the quinones were muchlower than that of streptonigrin; the ID50 values of the quinones were higher than 0.15^g/ml. In particular, the ID50 value of the ort/b-quinoline quinone derivative, 8-methoxy-7-methyl-5,6-dihydroquinoline-5,6-dione, was as high as 16^g/ml, while the 50% inhibition of cell growth was seen in the presence of 0.0025^g/ml streptonigrin. The membranetransport of the quinones was evaluated by comparing the effects on oxygen consumption by mitochondria and oxidation of NADHby bacterial diaphorase, being proven not to be responsible for their lower cytotoxicities.

Regioselective Bromination of 5,8-Dimethoxyquinoline with N-Bromosuccinimide

“…When a solvent chosen from CCl 4 , CH 2 Cl 2 and CH 3 CN was used, a mixture of regioisomers (2a and 2b) was formed without notable selectivity. The apparently lower reactivity in case of CCl 4 may be a consequence of low solubility of NBS in CCl 4 . Surprisingly, the substantial increase in the regioselectivity (6.1:1) for C(7) over C(6) and moderate isolation yields (79%) of 2b was observed using THF as a solvent under otherwise identical conditions.…”

“…4,5 Since the chemistry and structure-activity relationships of the substituted quinoline-5,8-diones are major concerns of the previous reports, 7-bromoquinoline-5,8-dione is chosen as one of key intermediates to allow introduction of structural diversity. However, there are few examples of its preparations in the literature.…”

Synthesis and Reactions of a New Quinone Quinoline 7‐(Carboxymethoxy)‐3‐sulfoquinoline‐5,6‐dione

“…In some works , quinoline‐5,6‐diones were used as intermediate compounds in the synthesis of polycyclic heteroaromatics. Interest in quinoline‐5,6‐diones and related compounds was stimulated by their relationship to the presumed biological activities ortho‐quinonoid compounds .…”

Sannanine, a new cytotoxic alkaloid from Streptomyces sannanensis

“…Additional preparative HPLC (Waters SunFire C18 10 mm (Milford, MA, USA) 19Â250 mm, flow rate: 10 ml min À1 ), eluted with water-methanol of gradient 6:4, yielded 50 mg of compound 1 H and 13 C NMR data suggested that 1 possesses quinoline-5, 8-dione skeleton, 1,2 which is the basic structural moiety for a kind of significant compound with wide biological activities. [5][6][7][8][9] By comparing the 1 H and 13 C data with the known compound 6-amino-2-methyl-quinoline-5,8-dione, 1 two more methyl groups were presented in the molecule of 1. HMBC correlations were observed between CH 3 (d¼2.40) and C-2 (d¼164.2), C-3 (d¼135.3), C-4 (d¼134.2), CH 3 (d¼2.69) and C-2 (d¼164.2), C-3 (d¼135.3), CH 3 (d¼2.93) and C-6 (d¼148.3), suggesting that two singlet methyls were located at C-2 and C-3, respectively, and the doublet methyl was linked with the amino group.…”

“…2,3 Over the past few decades, major research has focused on the synthesis and biological activities of variously 6,7-functionalized quinoline-5,8-diones. [4][5][6][7][8][9] In the course of screening for new antitumor bioactive compounds from microbial sources, a new cytotoxic quinoline-5,8-dione derivative, sannanine (1), was isolated from the fermentation broth of Streptomyces sannanensis (Figure 1). In this paper, we report the fermentation, isolation, structural elucidation and biological activities of 1.…”