Biochemical and pharmacologic studies with 1-β-d-arabinofuranosylcytosine 5′-adamantoate (NSC-117614), a depot form of cytarabine

Neil, Gary L.; Buskirk, Harold H.; Moxley, T. E.; Manak, R. C.; Kuentzel, Sandra L.; Bhuyan, Bijoy K.

doi:10.1016/0006-2952(71)90434-5

Cited by 27 publications

(12 citation statements)

References 8 publications

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“…Ara-C is rapidly converted to the inactive product uracil arabinoside by cytidine deaminase (1,2). On the other hand, cyclo-C (21, 30) is resistant to the deaminase, as are 5'-O-acyl derivatives of Ara-C (18). Therefore, it is of interest to determine whether 3'-esters of cyclo-C and Ara-C are also inactivated by cytidine deaminase.…”

Section: Resultsmentioning

confidence: 99%

“…Prevention of the antiviral activities of 3'-and 5'-acylates by eserine sulfate. The question was raised as to whether hydrolysis of 3'-0-acyl Ara-C to Ara-C is required for antivi-ral activity as has been suggested for 5'-O-acyl Ara-C (18). To solve this problem we tested whether the antiviral activity of the compound is inhibited by the addition of eserine sulfate (physostigmine sulfate, Merck), a choline esterase inhibitor, to the assay system.…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, in contrast to the resistance of 5'-esters of Ara-C to pyrimidine nucleoside deaminase, the 3'-esters were metabolized by a mouse kidney homogenate to an inactive product. Neil et al (18) have reported that inhibition of enzymatic hydrolysis with eserine sulfate, an esterase inhibitor, markedly reduced the cytotoxicity of 1-f&3--arabinofuranosylcytosine 5'-admantoate (Ado-Ara-C) against L1210 cells in culture and concluded that hydrolysis of Ado-Ara-C to Ara-C is required for cytotoxic activity. We also observed the same effect, i.e., the antiviral activity of 5'-O-decanoyl Ara-C being markedly reduced by the addition of eserine sulfate.…”

Section: Discussionmentioning

confidence: 99%

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Antiviral Activities of Acyl Derivatives of 2,2′-Anhydro-1-β- d -Arabinofuranosylcytosine and 1-β- d -Arabinofuranosylcytosine in Cell Culture

Sato

Nomura

Moffatt

1977

Antimicrob Agents Chemother

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Antiviral activities of acyl derivatives (3′- O -octanoyl and 3′- O -decanoyl) of 2,2′-anhydro-1-β- d -arabinofuranosylcytosine (cyclo-C) and 1-β- d -arabinofuranosylcytosine (Ara-C) were compared with other antiviral nucleosides, and some biological characteristics of the antiviral activity were investigated. Among those synthesized acyl derivatives, 3′- O -decanoyl ara-C was the most active against deoxyribonucleic acid viruses, with an activity comparable to that of Ara-C. Acyl derivatives of cyclo-C were somewhat less active than their Ara-C counterparts. In the value of therapeutic index, 1-β- d -arabinofuranosyladenine was superior to the others, followed by 5-iodo-2′-deoxyuridine. In comparing the sensitivity of two serotypes of herpes simplex virus it was found that Ara-C and its ester, as well as its cyclo-C counterpart, were more active against the type 2 than the type 1 strain. The activity of 3′- O -decanoyl Ara-C, like that of its parent, was diminished by treatment with cytidine deaminase from mouse kidney, but 3′- O -decanoyl cyclo-C was resistant to this treatment. In comparative studies of 3′- and 5′- O -acyl Ara-C's, antivaccinia virus activity of 3′- O -palmitoyl Ara-C was significantly superior to its 5′-counterpart. The inhibitory activity of 5′- O -decanoyl Ara-C was markedly reduced by the presence of a threefold molar excess of eserine sulfate, a choline esterase inhibitor, whereas the 3′-acyl Ara-C was not affected by the inhibitor in any combination. This result indicates that enzymatic hydrolysis of the 3′-ester to Ara-C, which is inhibited by eserine sulfate, did not occur in this cell culture.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Antiviral Activities of Acyl Derivatives of 2,2′-Anhydro-1-β- d -Arabinofuranosylcytosine and 1-β- d -Arabinofuranosylcytosine in Cell Culture

Sato

Nomura

Moffatt

1977

Antimicrob Agents Chemother

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“…An additional hazard now attaches to the foreThe activity of araC in L1210 leukemic mice is going. It has long been known that murine leukemia enhanced upon simultaneous administration of virus (MLV) may be 'activated' in mice by aging, car-3,4,5,6_tetrahydrouridine, a known potent inhibitor s52 of cytidine deaminase [70]. Additional deaminase inhibitors have been developed, such as N4-hydroxy-S-methyl-2'-deoxycytidine [71].…”

Section: Hazards Associated With Nucleoside Antiviral Agentsmentioning

confidence: 99%

Progress with antiviral agents

Shugar

1974

FEBS Letters

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“…Several derivatives of ara-C, such as cyclocytidine, 13) ara-C-5'-ester, [14][15][16]) N 4 -acyl-ara-C,17,18) and 5'-(3-snphosphatidyl)-ara-C 19 ) have been chemically synthesized.…”

mentioning

confidence: 99%

Formation ofβ-Galactosyl Compounds of Arabinosylcytosine in Growing Culture ofSporobolomyces singularis

Suzuki

Uchida

1994

Bioscience, Biotechnology, and Biochemistry

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Biochemical and pharmacologic studies with 1-β-d-arabinofuranosylcytosine 5′-adamantoate (NSC-117614), a depot form of cytarabine

Cited by 27 publications

References 8 publications

Antiviral Activities of Acyl Derivatives of 2,2′-Anhydro-1-β- d -Arabinofuranosylcytosine and 1-β- d -Arabinofuranosylcytosine in Cell Culture

Antiviral Activities of Acyl Derivatives of 2,2′-Anhydro-1-β- d -Arabinofuranosylcytosine and 1-β- d -Arabinofuranosylcytosine in Cell Culture

Progress with antiviral agents

Formation ofβ-Galactosyl Compounds of Arabinosylcytosine in Growing Culture ofSporobolomyces singularis

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