Disease relevance of NSC7664

• Thus, the acridone scaffold, when appropriately functionalized, can yield compounds with selective activity against pestiviruses and related viruses such as the HCV [1].
• Acridone synthase II cDNA was cloned from irradiated cell suspension cultures of Ruta graveolens L. and expressed in Escherichia coli [2].
• Studies on the inhibitory effects of some acridone alkaloids on Epstein-Barr virus activation [3].
• These results suggest that the acridone derivatives suppress HIV-1 replication at the transcriptional level primarily through a mechanism of PKC inhibition [4].
• The acridone derivatives were also tested against human cytomegalovirus (HCMV) replication but none of them were active [5].

High impact information on NSC7664

• ER-27319, an acridone-related compound, inhibits release of antigen-induced allergic mediators from mast cells by selective inhibition of fcepsilon receptor I-mediated activation of Syk [6].
• (iii) Indirect product labeling of released aldehyde groups by hydrazone formation with an acridone-labeled hydrazide [7].
• Novel compounds, composed of two acridone moieties connected by a propyl or butyl spacer, were synthesized and tested as potential modulators of P-glycoprotein (P-gp)-mediated multidrug resistance [8].
• The synthesis of two groups (Chart 1, types A and B) of conjugates of MDP (muramyldipeptide) and nor-MDP (normuramyldipeptide) with acridine/acridone derivatives and the synthesis of analogues of desmuramylpeptides (Chart 1, types C and D) containing acridine/ acridone derivatives have been described [9].
• A detailed structure-activity relationships (SAR) of these acridone derivatives were also studied [10].

Biological context of NSC7664

• These results indicate that, based on urinary excreted metabolites, the major biotransformation reactions for DACA in humans involve N-oxidation of the tertiary amine side chain and acridone formation, both of which appear to be detoxication reactions [11].
• New acridone inhibitors of human herpes virus replication [12].
• Interestingly, Hu. serrata polyketide synthase 1 lacks most of the consensus active site sequences with acridone synthase from Ruta graveolens (Rutaceae) [13].

Anatomical context of NSC7664

• The uptake of a substituted acridone by rat mast cells in relationship to histamine release: a possible indicator of exocytosis-induced expansion of the plasma membrane [14].
• These data indicate that acridone formation previously observed in isolated rat hepatocytes and in vivo is most likely due to aldehyde oxidase rather than cytochrome P450 [15].
• (Rutaceae) and of two further acridone alkaloids (arborinine and evoxanthine) were investigated by means of the MTT assay, using the human cell lines HeLa, MCF7 and A431 [16].
• Biliary excretion of AC metabolites (examined after removal of the gallbladder at the appropriate times) is greatest at 1-2 hr after treatment when at least 14 products are detected, including AC, AC-N-oxide, and other products with UV/visible spectra characteristic of ring hydroxylated and/or acridone derivatives [17].
• Further experiments documented the capacity for augmentation of airspace NK cell activity by intratracheal instillation of interferon inducers poly I:C and carboxymethyl acridanone [18].

Associations of NSC7664 with other chemical compounds

• Synthesis of the acridone alkaloids glyfoline and congeners. Structure-activity relationship studies of cytotoxic acridones [10].
• Autoxidation of the phosphonate carbanions derived from 9-phosphono-10-hydroacridanes provided chemiluminescence ascribed to the excited acridone anion [19].
• ACSs and CHSs had been cloned from Ruta graveolens and shown to be closely related polyketide synthases which use N-methylanthraniloyl-CoA and 4-coumaroyl-CoA, respectively, as the starter substrate to produce the acridone or naringenin chalcone [20].
• No NADPH-dependent acridone formation was observed with the microsomal fraction [15].
• Specificities of functionally expressed chalcone and acridone synthases from Ruta graveolens [21].

Gene context of NSC7664

• Two acridone synthase cDNAs (ACS1 and ACS2) have been cloned from Ruta cell cultures, and we report now the cloning of three chalcone synthase cDNAs (CHS1 to CHS3) from immature Ruta flowers [21].
• The metabolism of DACA to acridone metabolites by aldehyde oxidase (AO) (EC 1.2.3.1) appears to play a major role in its elimination in human patients and rodents [22].
• Selective inhibition of MDR1 P-glycoprotein-mediated transport by the acridone carboxamide derivative GG918 [23].
• Acridone synthase (ACS) and chalcone synthase (CHS) catalyse the pivotal reactions in the formation of acridone alkaloids or flavonoids [20].
• The molecular mass of acridone synthase II was estimated from size exclusion chromatography on a Fractogel EMD BioSEC (S) column at about 45 kDa, as compared to a mass of 44 +/- 3 kDa found for the acridone synthase I on Superdex 75 [2].

Analytical, diagnostic and therapeutic context of NSC7664

• Nevertheless, the sedimentation analysis by ultracentrifugation revealed molecular masses of 81 +/- 4 kDa for both acridone synthases [2].
• Molecular cloning and heterologous expression of acridone synthase from elicited Ruta graveolens L. cell suspension cultures [24].
• Nevertheless, our results suggest that very minor changes in the sequences of Ruta CHS genes are sufficient to also accommodate the formation of acridone alkaloids, which will be investigated further by site-directed mutagenesis [21].
• Chemico-enzymatic synthesis of a new fluorescent-labeled DNA by PCR with a thymidine nucleotide analogue bearing an acridone derivative [25].
• This study investigates the effects of 3 chemosensitizers (the cyclosporin analogue SDZ PSC 833 (PSC 833), the acridone carboxamide derivative GG 918, and verapamil) on the chemotherapy of HB in vitro [26].

References