Synthesis and antitumor properties of new glycosides of daunomycinone and adriamycinone

Arcamone, F; Penco, Sergio; Vigevani, A.; Redaelli, S.; Franchi, G; A, Dimarco; Casazza, Anna Maria; Dasdia, T; Formelli, Franca; Necco, A.; Soranzo, Carla

doi:10.1021/jm00241a013

Cited by 194 publications

(49 citation statements)

References 2 publications

(4 reference statements)

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“…Studies on the structure-activity relationships have indicated that some structural features of these antitumour antibiotics are important determinants for their binding to DNA. It has been shown (Arcamone et al, 1975;Zunino et al, 1972) that modifications in the amino sugar moiety, as well as in the aglycone moiety can change the ability of these molecules to bind to DNA and eventually their biological properties.…”

mentioning

confidence: 99%

Mutagenic and cytotoxic activity of doxorubicin and daunorubicin derivatives on prokaryotic and eukaryotic cells

Babudri¹,

Pani²,

Tamaro³

et al. 1984

Br J Cancer

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Summary The mutagenic and cytotoxic activity of two newly synthesized doxorubicin derivatives and of one daunorubicin derivative were studied in V79 Chinese hamster cells and bacteria (Salmonella typhimurium and Escherichia coli). The results showed that all the compounds tested were cytotoxic and mutagenic for both prokaryotic and eukaryotic cells. However, in both systems, the two 4-desmethoxy-and the 4'-desoxyderivatives were more active than the parent compounds, indicating that modifications in the aglycone or in the sugar moiety can produce appreciable changes in the biological properties of the anthracycline antibiotics. The in vitro activities observed in this study correlated with the in vivo antitumour potency.

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confidence: 99%

Mutagenic and cytotoxic activity of doxorubicin and daunorubicin derivatives on prokaryotic and eukaryotic cells

Babudri¹,

Pani²,

Tamaro³

et al. 1984

Br J Cancer

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“…Many anlinosugars and related antibiotics interfere with protein synthesis (7) and their bacterial toxicities could be greatly modified by manipulating the stereocheinistry or re~noving o111y one hydroxyl group in the niolecule (8). Furthermore, the reported reduced toxicity to cultured heart cells of 4'-epiadriamycin (9) pointed to the importance of the aminosugar 4-deoxydaunosamine (7) in attempts to reduce cardiotoxicity of this group of drugs.…”

Section: Common Vet Very Undesirable Side Effects Is Theirmentioning

confidence: 99%

The total synthesis of 4-deoxy-D,L-daunosamine

Hung¹,

Lam²,

Niemczura³

et al. 1978

Can. J. Chem.

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The aminosugar 4-deoxy-D,L-daunosamine and its derivatives were synthesized starting with 2,4-pentanedione which was converted to the key intermediate oxazolino-α-pyrone (19) by enamine formation with morpholine, oxidation with benzoyl peroxide, condensation with ammonium acetate, bromination with N-bromosuccinimide, nitrile formation, acid hydrolysis, and cyclization with thionyl chloride. Hydrogenation of 19 gave the δ-lactone 22 which was converted to 4-deoxy-D,L-daunosamine derivatives by reducing the lactone ring to the corresponding hemiacetal 26.

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“…Intensive and promising efforts are currently directed in several laboratories towards the development of semisynthetic, modified analogs of daunorubicin and adriamycin which might display increased efficacy or lower cardiopathogenicity, a cumulative, dose-related side-effect (3) that curtails the administration of the natural drugs. To this end, a large variety of analogs modified in the sugar portion have been synthesized and, in part, evaluated pharmacologically (4)(5)(6)(7)(8)(9)(10). Among the substitutes for daunosamine whose attachment to…”

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confidence: 99%

“…4-Deoxy-N-trifluoroacetyldaunosamine (13) has been prepared previously in a four-step reaction sequence from methyl N-trifluoroacetyldaunosaminide which, in turn, had been elaborated from natural daunorubicin (5,6 15 R = Me, X = picrate 11 R = E t , X = CI 16 R = E t , X = CI daunosamine for which there is now available a practical method of preparation starting from methyl a-D-mannopyranoside and comprising 9 steps (14). A multistep, achiral synthesis of racemic, 4-deoxy-D,L-daunosamine has also been achieved (15).…”

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confidence: 99%

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Synthesis of 4-deoxydaunosamine and 4-deoxyristosamine

Baer¹,

Hanna²

1980

Can. J. Chem.

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Treatment of methyl 3,6-dideoxy-2,4-di-O-methylsulfonyl-3-nitro-α-L-glucopyranoside (2) with sodium acetate and acetic acid in acetone gave methyl 4-O-acetyl-2,3,6-trideoxy-3-nitro-α-L-erythro-hex-2-enopyranoside (3) as a kinetic product, and the 2-O-acetyl-3,4,6-trideoxy-3-nitro-α-L-threo-hex-3-eno isomer 4 as the thermodynamically preferred product. Treatment of 2 or 4 with sodium borohydride produced a separable mixture of methyl 2,3,4,6-tetradeoxy-3-nitro-α-L-threo-hexopyranoside (5) and its α-L-erythro epimer (6), the latter being convertible into the former by base-catalyzed epimerization. Acid hydrolysis of 5 and 6 afforded the corresponding free nitro sugars 7 and 8. Catalytic hydrogenation of 5 led to the corresponding amino glycoside, isolated as the acetate 9 or hydrochloride 10; similarly, 6 gave the epimeric amine which was isolated as its acetate 14 or picrate 15. N-Trifluoroacetylation of 9 provided the N-trifluoroacetyl glycoside 12 which was hydrolyzed to give a 49% yield (overall from 2) of 2,3,4,6-tetradeoxy-3-trifluoroacetamido-L-threo-hexose (4-deoxy-N-trifluoroacetyldaunosamine, 13). Analogously, 14 afforded the epimeric N-trifluoroacetyl glycoside 17 which was hydrolyzed to give a 28% overall yield of 2,3,4,6-tetradeoxy-3-trifluoroacetamido-L-erythro-hexose (4-deoxy-N-trifluoroacetylristosamine, 18).

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Synthesis and antitumor properties of new glycosides of daunomycinone and adriamycinone

Cited by 194 publications

References 2 publications

Mutagenic and cytotoxic activity of doxorubicin and daunorubicin derivatives on prokaryotic and eukaryotic cells

Mutagenic and cytotoxic activity of doxorubicin and daunorubicin derivatives on prokaryotic and eukaryotic cells

The total synthesis of 4-deoxy-D,L-daunosamine

Synthesis of 4-deoxydaunosamine and 4-deoxyristosamine

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