Phosphonoformic acid antiviral activity

Phosphonoformic acid (Foscarnet), an antiviral drug, which consists of carboxylic acid and phosphate linked together, was shown to be absorbed in the small intestine by the phosphate carrier-mediated mechanism [154], The transport of folic acid was investigated in biopsy specimens of intestinal mucosa from healthy volunteers. A pH-dependent, active transport of folic acid was found in the proximal small intestine, whereas in the mucosa of the colon, folic acid uptake was driven by a facilitated diffusion, mediated by a low-affinity carrier [155]. The existence of folate receptors in the human colonic mucosa is logical due to the large amounts of folic acid produced by the colonic flora [145],... 

Lambert, R.W., Martin, J.A., Thomas, G.J., Duncan, I.B., Hall, M.J., and Heimer. E.P., Synthesis and antiviral activity of phosphonoacetic and phosphonoformic acid esters of 5-bromo-2 -deoxyuridine and related pyrimidine nucleosides and acyclonucleosides, J. Med. Chem., 32. 367, 1989. 

Some aromatic thiosemicarbazones are active against smallpox virus, while phosphonoformic acid (PFA) and phosphonoacetic acid (PAA) are active against herpes viruses. Consequently, some acylphosphonate thiosemicarbazones, (47), in which the two types of structural moieties appear together, were synthesized and tested for antiviral activity. However, no inhibitory activity was observed against herpes and/or pox viruses . 

A substantial number of phosphonates have been prepared and tested against viral infections, including AIDS. Even relatively simple compounds such as the above-mentioned phosphonoformic acid (19, = 0) and phosphonoacetic acid (19, n= 1) were reported as antivirals and herpes virus inhibitors active against acyclovirresistant herpes and cytomegalovirus retinitis in patients with AIDS . The veterinary use has been mentioned ... 

These two compounds may possess some clinical advantage over ara-A due to their low systemic toxicity. The antiviral effects of phosphonoformic acid (PFA, foscarnet sodium), which is presently in Phase III clinical trials in Europe, 3 have been discussed in a recent review.91 The synthesis and structural requirements for antiherpes activity of a series of PFA esters have also been reported.92... 

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