Syntheses of Idarubicin Analogues Containing a Glucose or Galactose Moiety as a Glycone

Abstract

The new idarubicin analogues (12 and 13) with a glucose or galactoseas as a glycone were synthesized from daunomycin (2). (+)-4-Demethoxydaunomycinone (6) obtained from reaction of 2 with AlCl3 was converted to 4-trifluoromethanesulfonyl daunomycinone (7) through reaction with trifluoromethanesulfonic anhydride. The treatment of 7 with 1,1-bis-(diphenylphospino)ferrocene/Pd(OAc)2 in triethylamine/formic acid/dioxane provided the idarubicinone (5b). Glycosylation of 7-hydroxy group of 5b with two kinds of tetraacetyl pyranosyl halide (8 and 9) by a modified Koenigs-Knorr procedure and then deacetylation using aqueous 0.1 N LiOH solution and amberlite cationic resin gave the objective materials. The in vitro MTT assay of the analogues (12b and 13a) in comparison with idarubicin (5a) on peripheral blood human promyelocytic-leukemia cell line and human breast cancer cell line were also described.Key Words: Anthracycline, Idarubicin, Idarubicinone, Glucose, Galactose

Solvation of 1-Amino-4-Hydroxy-9,10-Anthraquinone Governs Its Electrochemical Behavior in Non-Aqueous and Aqueous Media: A Cyclic Voltammetry Study

“…Efforts are therefore on to find out new but cheaper analogues and derivatives of anthracycline drugs. In several studies [11][12][13][14][15][16] we were able to show that much cheaper hydroxy-9, 10-anthraquinones mimic the behavior of anthracycline drugs. A very recent study by Rossi et al 17 showed that 1, 4-dihydroxy-9, 10-anthraquinone and 1, 8-dihydroxy-9,10-anthraquinone have promising anticancer activity though they do not posses any sugar moiety.…”

“…Although several studies on hydroxy-9, 10-anthraquinones [11][12][13][14][15][16] and mitoxantrone (an amino hydroxy-9, 10-anthraquinone) [18][19][20][21][22] were extensively carried out the other amino hydroxy-9,10-anthraquinones have not been seriously investigated as a possible substitute of anthracycline anticancer drugs.…”

1-Amino-4-hydroxy-9,10-anthraquinone – An analogue of anthracycline anticancer drugs, interacts with DNA and induces apoptosis in human MDA-MB-231 breast adinocarcinoma cells: Evaluation of structure–activity relationship using computational, spectroscopic and biochemical studies

“…Therefore, efforts are presently afoot to evaluate new but comparatively less expensive substitutes of the known forms of these drugs. Through several studies [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , we and others were able to develop less expensive hydroxy-anthraquinone-mimetic drugs. Rossi and coworkers [17] showed that two variant hydroxy-anthraquinones that do not posses any sugar moiety to exhibit significant chemotherapeutic efficiency.…”

Spectroscopic, computational and electrochemical studies on the formation of the copper complex of 1-amino-4-hydroxy-9,10-anthraquinone and effect of it on superoxide formation by NADH dehydrogenase

“…Most of the studies on anthracyclines and their metal complexes mention their interaction with DNA either in vitro or in vivo. [5][6][7][8][9][10][11] Although there are many applications of anthracyclines in chemotherapy, these drugs, being very costly, may find a hindrance to their use in patients of economically challenged countries. This is most unfortunate and needs serious consideration.…”

“…20 Mitoxantrone induces compaction of isolated chromatin 21 and protein-associated DNA cleavage 22 and inhibits DNA and RNA synthesis. Although studies on hydroxy-9,10-anthraquinones [11][12][13][14][15][16][17][18] and mitoxantrone [19][20][21][22][23][24] have been extensively carried out, amino-hydroxy-9,10-anthraquinones have not yet been seriously investigated as a possible substitute and hence the present study has been carried out on 1-amino-4-hydroxy-9,10-anthraquinone.…”