Studies on the antileukemic action of certain compounds related to moieties of the 4-amino-pteroylglutamic acid (aminopterin) molecule

✍ Scribed by Howard E. Skipper; Pradisth C. Edwards; Carl E. Bryan; Juanita B. Chapman; Martelia Bell; Olivia S. Hutchison

• Publisher: John Wiley and Sons
• Year: 1950
• Tongue: English
• Weight: 258 KB
• Volume: 3
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/1097-0142(1950)3:2<348::aid-cncr2820030217>3.0.co;2-n

✦ Synopsis

first reported the palliative effects of 4-amino-pteroylglutamic acid in acute leukemia of children. Burchenal and associates2 observed that this compound and its "0-methyl analogue possessed the ability to prolong survival time of mice with a rather acute strain (Ak 4) of transplanted leukemia. These pteroylglutamic acid (PGA) derivatives, as well as other variations of PGA, have been shown to be PGA antagonists in certain bacteria.3

A number of pteridines have been synthesized and tested for PGA antagonism in bacteria.4 Several were found to possess this activity, but to a lesser degree than the 4-amino-pteroylglutamic acids.

Zarafonetis et al. noted that large doses of the sodium salt of p-aminobenzoic acid (PABA) caused a striking lowering of the leukocyte counts in five patients with chronic myelogenous leukemia and in one patient with subacute myelogenous leukemia. This palliative effect of PABA promptly disappeared when the treatment was stopped. It has been observed6 that 2,4-and 3,4diaminobenzoic acid show a bacteriostatic action that can be counteracted by PABA, and that, like PABA, 2-chloro-4-amino-and 2-bromo-4-aminobenzoic acid are able to annihilate the bacteriostatic action of sulfanilamide. This report of work by Backer