Acridone Derivatives Research Articles

Synthesis and activity against multidrug resistance in Chinese hamster ovary cells of new acridone-4-carboxamides.

A number of tricyclic carboxamides have been synthesized and tested to evaluate their ability to reverse multidrug resistance in the CHRC/5 cell line. Among them the acridone derivatives were the most potent. A key feature is the presence of a dimethoxybenzyl or phenethylamine cationic site, separated from the tricyclic lipophilic part by a carbamoylphenyl chain. Optimization led to compounds 2 orders of magnitude more active than the prototype inhibitors verapamil and amiodarone. On the basis of in vitro and in vivo activities, 9,10-dihydro-5-methoxy-9-oxo-N-[4-[2-(1,2,3,4-tetrahydro-6,7- dimethoxyisoquinol-2-yl)ethyl]phenyl]-4-acridinecarboxamide (84) has been selected for further development.

ChemInform Abstract: A New Class of Antitumor Agents: Conjugates of MDP and Acridine/ Acridone Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Rat hepatocyte-mediated metabolism of the experimental anti-tumour agent N-[2'-(dimethylamino)ethyl]acridine-4-carboxamide.

1. Metabolism of the experimental antitumour agent N-[2'-(dimethylamino)-ethyl]acridine-4-carboxamide (AC) has been studied in isolated rat hepatocytes using 3H-AC. 2. The major primary metabolites of AC (150 microM) are the 9(10H)acridone, N-oxide and N-monomethyl derivatives. The equivalent 9(10H)acridone derivatives are also formed from AC-N-oxide and N-monomethyl-AC followed by formation of the 7-hydroxy-9(10H)acridone derivatives of AC and N-monomethyl-AC. A similar pattern of metabolism was observed on incubation of AC-N-oxide. 3. Inhibition studies with SKF 525A (250 microM) and methimazole (250 microM) indicate that N-demethylation is mainly catalysed by cytochrome P450 whereas N-oxidation is mediated mainly by flavin-containing monooxygenases. Both primary and secondary acridone formation were also inhibited by SKF 525A as was the back-reduction of AC-N-oxide to AC. 4. These results show that the rat hepatocyte system is a suitable model for further characterization of the metabolism of AC.

Structures of two crown-ether derivatives of 9-acridone

(I) N-Methyl-2,5,8,11,14,17,20-heptaoxa-25-azatetracyclo[19.7.5.0(24,32),0(26,30)]tritriaconta-1 (29),-21(33),22,24(32),26(30),27-hexaen-31-one trihydrate, C26H33NO8.3H2O, M(r) = 541.6, triclinic, P1BAR, a = 7.389 (1), b = 13.255 (1), c = 14.448 (2) angstrom, alpha = 88.60 (1), beta = 78.58 (1), gamma = 81.48 (1)-degrees, V = 1371.7 (2) angstrom 3, Z = 2, D(x) = 1.31 g cm-3, lambda(Cu K-alpha) = 1.54178 angstrom, mu = 8.68 cm-1, F(000) = 580, T = 291 K, R = 0.047 for 3376 observed reflections. (II) N-Methyl-2,5,8,11,14,17-hexaoxa-22-azatetracylco[16.7.5.0.(21,29).0(23,27)]triaconta-1 (26), 18(30), 19,-21(29),23(27),24-hexaen-28-one, C24H29NO7, M(r) = 443.5, triclinic, P1BAR, a = 8.426 (2), b = 11.420 (2), c = 11.739 (4) angstrom, alpha = 87.20 (3), beta = 79.33 (3), gamma = 77.88 (2)-degrees, V = 1085.3 (5) angstrom 3, Z = 2, D(x) = 1.36 g cm-3, lambda(Mo K-alpha) = 0.71069 angstrom, mu = 1.08 cm-1, F(000) = 472, T = 291 K, R = 0.039 for 3229 observed reflections. In these substituted acridone derivatives one molecule contains both a crown ether moiety with its complexing capabilities and a heterocyclic N atom able to modify these properties. In the two compounds, the crown ether chain is nearly perpendicular to the acridinic skeleton which is planar. In (I) the water molecules take part in hydrogen bonds with the crown ether [O37...O11 = 3.03 (1), O35...O36 = 2.81 (1) angstrom] and with each other [O36...O37 = 2.93 (1), O38...O36 = 2.84 (1), O38...O37 (x + 1, y, z) = 2.89 (1) and O38...O37 (1 - x, 1 - y, 1 - z) = 2.88 (1) angstrom]. The bond lengths suggest partial localization of double bonds in the benzene rings.

Natural product chemisrty, 143. Convenient synthesis of isoacronycine and some other new acridone derivatives

AbstractThe iodination of 1,3‐dihydroxy‐9‐acridone (1), 1‐hydroxy‐3‐methoxy‐10‐methyl‐9‐acridone (2) and 1,3‐dihydroxy‐10‐methyl‐9‐acridone (3) yields 1,3‐dihydroxy‐2,4‐diiodo‐9‐acridone (4), 1‐hydroxy‐2‐iodo‐3‐methoxy‐10‐methyl‐9‐acridone (5) and 1,3‐dihydroxy‐2‐iodo‐10‐methyl‐9‐acridone (6), respectively. The methylation of 4 and 5 gives 2,4‐diiodo‐1,3‐dimethoxy‐10‐methyl‐9‐acridone (7) and 2‐iodo‐1,3‐dimethoxy‐10‐methyl‐9‐acridone (9), respectively. The direct CC coupling of 2‐methyl‐3‐buten‐2‐ol to the compounds 5, 7 and 9 by palladium catalysed Heck condensation method gives three new acridone derivatives 1‐hydroxy‐2‐(3‐hydroxy‐3‐methyl‐1‐butenyl)‐3‐methoxy‐10‐methyl‐9‐acridone (10), 2,4‐bis(3‐hydroxy‐3‐methyl‐1‐butenyl)‐1,3‐dimethoxy‐10‐methyl‐9‐acridone (12) and 2‐(3‐hydroxy‐3‐methyl‐1‐butenyl)‐1,3‐dimethoxy‐10‐methyl‐9‐acridone (13) while compound 6 is converted into isonoracronycine (11). The methylation of 11 yields isoacronycine (14).

2-Trialkylstannyl derivatives of acridone, phenanthridone, and anthraquinone

1. The cross coupling reaction of hexaalkyldistannanes was carried out with 2-iodo-acridone, 2-bromoacridone, 2-bromophenanthridone, and 2-iodoanthraquinone catalyzed by palladium complexes. 2. The reaction proceeds in the presence of bromide ions in the case of acridone and phenanthridone derivatives.

Identification of conjugation and cleavage products in the thiolytic metabolism of the anticancer drug 4'-(9-acridinylamino)methanesulfon-m-anisidide.

Conjugation and cleavage products in the thiolytic metabolism of the anticancer drug 4'-(9-acridinylamino)methanesulfon-m-anisidide were identified primarily by high-pressure liquid chromatography in combination with field desorption mass spectrometry. The spontaneous metabolic pathway of the drug, as related to its susceptibility to nucleophilic attack by endogenous thiols at the 9-carbon atom of the acridine moiety, has been studied. Among the metabolite fraction of 4'-(9-acridinylamino)methanesulfon-m-anisidide excreted in rat bile after administration of a therapeutic dose, a conjugate was identified as the 9-acridinyl thioether of glutathione. This conjugation product and the corresponding 9-acridinyl conjugates were formed spontaneously after incubation of 4'-(9-acridinylamino)methanesulfon-m-anisidide with glutathione, cysteine and N-acetylcysteine in sodium phosphate buffer and other aqueous media, as established by high-pressure liquid chromatography and field desorption mass spectra. The thiolytic pathway results in the release 4-amino-3-methoxymethanesulfonanilide which was identified in all in vitro experiments and in rat serum after intravenous 4'-(9-acridinylamino)methanesulfon-m-anisidide. 9(10H)-Acridone, 9-aminoacridine and other acridine derivatives which occur as minor products during the thiolytic cleavage in vitro were identified by field desorption and partially by high resolution electron impact mass spectrometry.

13C-NMR-Spektren einiger Acridon-Derivate [1] / 13C NMR Spectra of Some Acridone Derivatives [1

Abstract The 13C NMR spectra of acridone derivatives 3-5, 8-12, melicopicine (14), melicopidine (15) and melicopine (16) are presented. The substituent parameters for OH and OCH3 groups in acridone derivatives have also been given.

A re-examination of Evodia alata F. Muell. The structure and synthesis of evoprenine, a new acridone alkaloid

The known alkaloids, evoxanthine, melicopidine, 1,2,3-trimethoxy-10- methylacridan-9-one, its 1-demethyl derivative, and kokusaginine have been isolated from the bark of Evodia data collected in New Guinea, together with a new alkaloid, evoprenine. By synthesis from evoxanthine, evoprenine was shown to be 1-hydroxy-2-methoxy-3-[(3- methylbut-2-enyl)oxy]-10-methylacridan-9-one. Some aspects of the N.M.R. and mass spectrometry of acridone derivatives are discussed.