Hepatic drug-metabolizing enzyme activity in rats pretreated with (−)-emetine or (±)-2,3-dehydroemetine

Miller, Harry H.; Johnson, Randall K.; Donahue, James P.; Jondorf, W. R.

doi:10.1042/bj1170491

Cited by 17 publications

(13 citation statements)

References 22 publications

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“…(-)-Isoemetine as predicted from its antipodal configuration at the C-l' position in the molecule [5] and the absence of activity in various model systems [15,25,32] is also inactive as an antileukemic agent in the mouse L1210 test system (table VII) when tested over a dose range on the Q4D, day 1, 5, 9 schedule. Other compounds lacking the correct stereospecific alignment at the C -l' position in the molecule (table VIII) are equally nontoxic and ineffective as antileukemic agents when tested on the same basis.…”

Section: Discussionmentioning

confidence: 99%

“…On the basis of previous experiments to clarify structure-activity rela tionships among emetine derivatives with regard to anti-amebic activity in vitro [15] and effects on protein biosynthesis [15,25] or drug metaboliz ing enzyme activity [32], it was easy to select other compounds that might exhibit antileukemic activity comparable to emetime. All the compounds tested, which had the required stereospecific alignment at the C -l' posi tion in the molecule [15] and a free secondary amine structure at the N-2' position ( fig.…”

Section: Discussionmentioning

confidence: 99%

“…(-)-Emetine and some of its active derivatives may be even more effective under appropriate circumstances. In view of the recent realization that (-)-emetine and ( ± )-2,3-dehydroemetine inhibit the metabolism of other drugs [26,32], care will have to be exercised in devising the optimal con ditions for combination chemotherapy [11] for leukemia where (^-eme tine or one of its active derivatives is included as a component of such combined therapy.…”

Section: Discussionmentioning

confidence: 99%

“…(B) (-)-Isoemetine, (C) (-)-2,3-dehydroemetine, (D) (+)-2,3-dehydroemetine, all according to Brossi el al. [5] and (E) naturally occurring tubulosine, R2 = H (according to M onteiro et al [33]) and O-methyltubulosine R2 = CH 3. parameters of protein biosynthesis in various systems [15,25] and on drug metabolizing enzyme activity in rats [32]. From these studies, it has become apparent that structural and stereospecific requirements for bio logical potency involve the correct stereochemical configuration at the asymmetric C-atom at the l'-position in the emetine molecule and a free secondary amine structure at the 2'-position as indicated in figure 1A.…”

Section: Introductionmentioning

confidence: 99%

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Increased Lifespan of Leukemic Mice Treated with Drugs Related to (–)-Emetine

et al. 1971

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The lifespan of mice bearing ascitic leukemia L1210 could be prolonged by treatment with (-)-emetine dihydrochloride. Optimal dosage schedules required emetine administration daily for 5 days (QD, day 1–5) or intermittently on every 4th day. (Q4D, day 1, 5, 9). Compounds related to (-)-emetine which are active in other biological systems, having the correct stereospecific structure at the C-1′ position in the molecule, a secondary amine structure at N-2′ and an ethyl-group substituent at C-3 were also effective in prolonging the survival time of L1210 leukemic mice. The effective compounds were (-)-cephaeline, (±)-2,3-dehydroemetine, (-)-2,3-dehydroemetine, (-)-tubulosine and (-)-O-methyltubulosine. In contrast, (-)-isoemetine and several derivatives of (±)-2,3-dehydroemetine, lacking the critical configuration at C-1′ or substitution at the N-2′ and C-3 positions in the molecule, were inactive in the mouse leukemia system, when administered according to the Q4D, day 1, 5, 9 schedule.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Increased Lifespan of Leukemic Mice Treated with Drugs Related to (–)-Emetine

et al. 1971

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“…When a bare Ag surface is anodically oxidized, the initial reaction is Ag going into solution, probably as the ion A g ( O H ) 2 -. The solution becomes supersaturated in the early part of a charge (7). Dissolved Ag precipitates on the Ag surface as Ag20.…”

Section: Discussionmentioning

confidence: 99%

The Microstructure of Sintered Silver Electrodes

Wales¹

1971

J. Electrochem. Soc.

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Ag electrodes were charged at the 20-hr rate of constant current and discharged at the 1-hr rate in 35% KOH solution at 25~Cross sections of samples cut from the electrodes during charges at cycles 1-30 were examined. Almost all Ag particles had a visible coating of Ag20 when an electrode was charged for half the capacity accepted at the Ag/AgeO potential plateau. The electrode surface had the same structure as the interior. In a cycled electrode approximately 60% of the Ag had been oxidized to Ag20 when the potential peak separating the Ag/Ag20 and Ag20/AgO plateaus was reached.The present paper describes structural changes in Ag electrodes as Ag20 was formed in an alkaline solution. The Ag electrodes were of the type used in Ag-Zn and Ag-Cd storage batteries.There have been two previous papers in this series concerning the microstructure of sintered Ag electrodes. The first paper described the structures present as charged electrodes were being reduced during discharges (1). The second described the structures present at the end of a series of complete discharges (2). The formation of AgO will be the subject of a later paper. The electrodes in this series of investigations were always discharged at the 1-hr rate and charged at the 20-hr rate of constant current in 35% KOH solution.When Ag electrodes are discharged in a KOH solution at a high current density for a series of cycles the electrode capacity is m a i n t a i n e d at a higher value than when a low discharge C.D. is used. This difference in capacity results from changes in the microstructure of the electrodes. The microstructure of a cycled electrode depends partly on the discharge C.D. that is used. A discharge at the relatively fast 1-hr rate results in formation of small Ag particles, m a n y having a size on the order of 1~. Particles of this size oxidize readily during the next charge. When the slow 20-hr discharge rate is used, however, most of the Ag particles that form are 10-25~ (3).Particles of Ag larger than 4 or at most 5~ do not oxidize completely during a charge. Oxidation usually stops before an oxide layer reaches a thickness of 2~. As a result, the central portion of large particles remains as metallic Ag at the end of a charge instead of being oxidized. Once large particles form in an electrode during a slow discharge, the original discharge capacity is not regained readily. When slow discharges are used, the capacity decreases so rapidly that by cycle 3 the electrodes always discharged at the 20-hr rate give less capacity than electrodes always discharged at the 1-hr rate. This occurs despite the fact that approximately 10% of the oxide remains at the end of a fast discharge, and almost all of the oxide is reduced during a slow discharge. Experimental ProcedureOnly a brief account of the experimental procedure will be given here, because it has already been described (1). Sintered Ag electrodes were cycled individually in an excess of 35% KOH solution at 25~ The Ag electrodes were charged using constant current at the 20-hr...

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Synthesis of Pyrido‐[2,1‐a]isoquinoline Derivatives via Gold(I)‐Catalyzed Intramolecular Cascade Reaction of Enamides

Xu,

Chen,

et al. 2023

Adv Synth Catal

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A gold(I)‐catalyzed intramolecular cascade reaction of tertiary enamides has been developed, which provides a method for the preparation of diverse pyrido[2,1‐a]isoquinoline derivatives with good function group tolerance. Preliminary investigation of the reaction mechanism indicate that this process comprises a nucleophilic addition of the enamide to an alkynyl group, followed by the capture of the acyliminium ion by an electron‐rich aromatic component. Additionally, scale‐up experiments and further transformations of pyrido‐[2,1‐a]isoquinolines underscore the utility of this methodology.

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Hepatic drug-metabolizing enzyme activity in rats pretreated with (−)-emetine or (±)-2,3-dehydroemetine

Cited by 17 publications

References 22 publications

Increased Lifespan of Leukemic Mice Treated with Drugs Related to (–)-Emetine

Increased Lifespan of Leukemic Mice Treated with Drugs Related to (–)-Emetine

The Microstructure of Sintered Silver Electrodes

Synthesis of Pyrido‐[2,1‐a]isoquinoline Derivatives via Gold(I)‐Catalyzed Intramolecular Cascade Reaction of Enamides

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