Folic acid compounds antagonists

Possibly the most significant discovery in the metabolism of aromatic azo compounds had implications that heralded the age of modem chemotherapy. It was shown that the bactericidal effect of the azo dye Prontosil in vivo was in fact due to the action of its transformation product, sulfanilamide, which is an antagonist of 4-aminobenzoate that is required for the synthesis of the vitamin folic acid. Indeed, this reduction is the typical reaction involved in the first stage of the biodegradation of aromatic azo compounds. 

Pyrimethamine is a folic-acid antagonist its therapeutic action is based on differential requirements between host and parasite for nucleic acid precursors involved in growth as it selectively inhibits plasmodial dihydrofolate reductase. Pyrimethamine inhibits the enzyme dihydrofolate reductase that catalyzes the reduction of dihydrofolate to tetrahydro-folate. This activity is highly selective against plasmodia and Toxoplasma gondii. It does not destroy gametocytes but arrests sporogony in the mosquito. Pyrimethamine possesses a blood schizonticidal, and some tissue schizonticidal activity may be slower than that of 4-amino-quinoline compounds. 

This ring system has attracted little interest as a source of compounds of possible pharmacological interest. The synthesis of the potential folic acid antagonist 81 has been described. Analogues of chloroquine such... 

It is the purpose of this paper to record the results of clinical and hematologic studies on 5 children with acute leukaemia treated by the intramuscular injection of a synthetic compound, 4-aminopteroylglu-tamic acid (aminopterin). This substance is an antagonist of folic acid regarding growth of Streptococcus faecalis R. ... 

The antimetabolites are structurally similar to endogenous compounds and are antagonists of folic acid (methotrexate), purines (mercaptopurine, thioguanine), or pyrimidines (fluorouracil, cy-tarabine). Antimetabolites are CCS drugs acting primarily in the S phase of the cell cycle. Their sites of action on DNA synthetic pathways are shown in Figure 55-3. In addition to their cytotoxic effects on neoplastic cells, the anti metabolites also have immunosuppressant actions. Some of the uses of the antimetabolites in neoplastic disease are listed in Table 55-2. 

Identification of Sulfonamide Compounds. Sulfonamide compounds are antagonists of the prokaryotic enzyme tetrahydropteroic synthetase hence, they inhibit the production of folic acid. By establishing a competition for the occupancy of the enzyme active site in the presence of the natural agonist, para-aminobenzoic acid (p-ABA), the antagonistic effect of the sulfonamides can be selectively reversed. ... 

Antimctabolite a compound so similar in structure to a metabolite that it occupies the same specific enzyme binding sites. This results either in inhibition of the enzyme or substitution of the A. for the metabolite in the reaction, possibly leading to incorporation of the A. into cell components. Both effects lead to metabolic disturbances or inhibition of cell division. Many A. are used therapeutically, e.g. analogs of purines and pyrimidines and folic acid antagonists are used as carcinostatic agents. 

Uses sun-screening agent in cosmetics, moisturizers, shampoos, hair-care products, nail polish, lipstick, lip balms, oral vitamin supplements manufacture of various esters (local anesthetics), folic acid and azo dyes in sunburn preventatives used in laboratories as sulfonamide antagonist antirickettsial Cross para groups of compounds. PA PABA A... 

This is a yellow crystalline compound used clinically as an antagonist to folic acid in the treatment of certain leukemias. 

Ophiostoma muUiannulatum (57) as well as the wild strain of Lactobacillus arabinosus (53) did utilize AICA, even though the compound was required in greater concentrations than purines for equivalent growth. AICA also accumulated when E. coli was grown in the presence of aminopterin (4-aminopteroylglutamic acid), a folic acid antagonist (58). Finally, a mutant of E. coli was isolated that produced AICA in the absence of added metabolite antagonists (59). 

Dichloromethotrexate (XXXII, mol. wt. 523) is a folic acid antagonist and its metabolism and excretion in the rat. dog, mouse, and rabbit have been studied using the C1-Iabeled compound (Oliverio and Davidson, 1962). Table XXIX shows that the three former species excrete about 60-80% of a dose of dichloromethotrexate in the bile, while the rabbit eliminates about 40% by this route. There is a species difference in the... 

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