Studies on Methylglyoxal Bis(guanylhydrazone)¹ Analogs. I. Homologs of Methylglyoxal Bis(guanylhydrazone)²

Abstract

MethylglyoxalBi.s-(gcanylhydrazoxes) 283 2-Methylthio-2-imidazoline Hydrochloride.-A mixture of 209.5 g. (2.05 moles) of ethylenethiourea, 120 ml. (2.36 moles) of methyl chloride, and 250 ml. of methanol was heated in a stainless steel bomb at 100°for 3 hr. The reaction mixture was filtered to obtain 196 g. of material melting at 166-169°. The filtrate was diluted with ether to obtain an additional 92.5 g. of product, m.p. 161-166°. Total yield was 288.5 g. (92%).

Chance factors in studies of quantitative structure-activity relationships

“…For 20 variables screened and only 15 observations, practically all of the runs resulted in some level of chance correlation with about 44% of the total runs resulting in a correlation with r2 > 0.8. As the number of observations increased to 30, the number of runs yielding correlations with r2 > 0.8 declined to about 1 %.…”

“…Again the depicted linear relationships are each statistically significant at the p < 0.0001 level. Thus, for 10 variables, 20 observations are needed at a chance correlation level of 1%, which reduces to 15 at the 5% level and 13-14 at the 10% level. Some limitations must be pointed out to the approach described in this study for estimating probable chance correlation levels.…”

Comparison of inhibitors of S-adenosylmethionine decarboxylase from different species

“…The final product contained about 2,umol of bound drug per ml of gel. Ethylglyoxal bis(guanylhydrazone) was a gift from Dr. E. Mihich, Roswell Park Memorial Institute, Buffalo, NY, U.S.A. Other preparations of this drug were synthesized by a published procedure (Podrebarac et al, 1963). Most of the structural analogues of AdoMet used in this study were generously provided by Dr. R. T. Borchardt, Department of Biochemistry, University of Kansas, Lawrence, KS, U.S.A. Their synthesis is described by Borchardt et al (1976).…”

Specific inhibition of the enzymic decarboxylation of S-adenosylmethionine by methylglyoxal bis(guanylhydrazone) and related substances

“…Unless otherwise stated, all reactions were initiated by the addition of the appropriate enzyme and suitable controls were invariably set up to correct for all non-enzymic reactions. Jjirudonine (diamidinospermidine) and arcaine (diamidinoputrescine) were generously given by Professor Seymour S. Cohen of the Department of Microbiology, University of Colorado School of Medicine, Denver, Col., U.S.A. Methylglyoxal bis-(guanylhydrazone) in the form of its dihydrochloride monohydrate, and bis(guanylhydrazone) derivatives of related glyoxals (Freedlander & French, 1958;Podrebarac et al, 1963;Podrebarac & Cheng, 1964) were obtained through the courtesy of Dr. Harry Wood of the Cancer Chemotherapy National Service Center of the National Cancer Institute, Bethesda, Md., U.S.A. All other substances were of commercial origin and of the highest grade of purity. Solutions of all drugs were prepared in water and were tested as enzyme inhibitors immediately.…”