The Carcinostatic Activity of Some 2-Amino-1,3,4-Thiadiazoles

Oleson, J. J.; Sloboda, Adolph E.; Troy, W. P.; Halliday, S. L.; Landes, M. J.; Angier, Robert B.; Semb, Joseph; Cyr, K.; Williams, James H.

doi:10.1021/ja01629a133

Cited by 62 publications

(30 citation statements)

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“…As in the case of 5-fluoroorotic acid, 6-mercaptopurine exhibits a diversity of actions, which include feedback inhibition of earlier stages of purine biosynthesis (19), and interference with the conversion of inosine-5'-phosphate to other purine nucleotides (20). The (24), exhibits a unique property of increasing uric acid synthesis in man unrelated to tissue destruction (25). Although the precise mechanism of its action has yet to be defined, indirect evidence suggests that it may participate as a nicotinamide analogue (26).…”

Section: Resultsmentioning

confidence: 99%

Pyrimidine Metabolism in Man. V. The Measurement in Vivo of the Biochemical Effect of Antineoplastic Agents in Animal and Human Subjects*

Rabkin¹,

Frederick²,

Lotz³

et al. 1962

J. Clin. Invest.

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Many in v'ivo studies have been carried out on purine metabolism in man because of the presence of a readily available end product, uric acid. In the absence of a comparable unique end product, no previous over-all measurements of pyrimidine metabolism in the intact organism have been reported. Studies have been limited to the excretion of /8-aminoisobutyric acid, as a metabolite of thymine (1), the incorporation of pyrimidine precursors into circulating leukocytes (2), the induced urinary excretion of orotic acid and orotidine (3), and the spontaneous urinary excretion of certain trace pyrimidines (4). In this report a method is described for evaluating pyrimidine nucleotide synthesis in the intact organism, based on the release of carbon dioxide-C14 from carboxyl-labeled pyrimidine precursors. The usefulness of this procedure in defining the onset, degree, and duration of action of certain antimetabolites is illustrated by studies in rats, and in patients with leukemia. MATERIALS AND METHODSIntravenous injections of labeled compounds were given through indwelling jugular vein catheters to male albino rats, weighing 125 to 150 g. For collection of expired C1402, air was flushed through a closed metabolic chamber and the carbon dioxide trapped in 3 N NaOH. Acidification of aliquots of this solution allowed trapping of the carbon dioxide in Hyamine base and counting in a Packard Tri-Carb liquid scintillation spectrometer at an efficiency of approximately 45 per cent. Indwelling cystostomy catheters were operatively placed in rats for urinary studies. Sedation with perphenazine (Trilafon, Schering), and hydration with normal or hypotonic saline *

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Section: Resultsmentioning

confidence: 99%

Pyrimidine Metabolism in Man. V. The Measurement in Vivo of the Biochemical Effect of Antineoplastic Agents in Animal and Human Subjects*

Rabkin¹,

Frederick²,

Lotz³

et al. 1962

J. Clin. Invest.

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“…thiazole and 1,3,4-thiadiazole have antitumor activity with excellent IG50 and IC50 as depicted in Figure 1 [33][34][35][36][37]. In view of these facts, we report herein the synthesis of a new series of thiazoles and 1,3,4-thiadiazoles bearing indole moiety for the examination of their antitumor activity against the MCF-7 human breast carcinoma cell line.…”

Section: -(1h-indol-3-yl)-3-(p-tolyl)prop-2-en-1-one (3a) [38] and 3mentioning

confidence: 93%

“…In light of these facts, we have synthesized some new thiazole, dihydropyrido [3,2-e] [1,2,4]triazolo [4,3-a]pyrimidine and 1,3,4-thiadiazole derivatives using 3-acetylindole as a common precursor and screened these compounds for their anticancer activities. A literature survey showed that many derivatives of thiazole and 1,3,4-thiadiazole have antitumor thiazole and 1,3,4-thiadiazole have antitumor activity with excellent IG50 and IC50 as depicted in Figure 1 [33][34][35][36][37]. In view of these facts, we report herein the synthesis of a new series of thiazoles and 1,3,4-thiadiazoles bearing indole moiety for the examination of their antitumor activity against the MCF-7 human breast carcinoma cell line.…”

Section: Introductionmentioning

confidence: 94%

Synthesis of New 3-Heteroarylindoles as Potential Anticancer Agents

et al. 2016

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“…2,5-Diamino-1,3,4 thiadiazole (DA-TDA), the compound of this group which has been found inactive against animal tumors (7)(8)(9), has been given in gradually increasing doses up to 2 Gm. daily, 10 times the highest dose of EA-TDA which has been employed (Table III).…”

Section: Irwin H Krakoff and M Earl Balismentioning

confidence: 99%

“…The purpose of this paper is to describe further experiences with this drug and related compounds. The anti-tumor effects of these agents in animals have been described previously (6)(7)(8)(9). Three compounds in this series have been studied in humans: 2-amino-1,3,4 thiadiazole; 2-ethylamino-1,3,4 thiadiazole; and 2,5 diamino-1,3,4 thiadiazole (Figure 1).…”

mentioning

confidence: 99%