Nalidixic acid, prodrugs

A potentially interesting application of (acyloxy)methyl ester prodrugs can be found in delivery through skin of antibacterial agents. Nalidixic acid (8.53, R = H), a topoisomerase II inhibitor, showed promising activity in the treatment of antiproliferative skin disorders, notably psoriasis. To improve the... 

Table 8.6. Chemical and Enzymatic Hydrolysis of Ester Prodrugs of Nalidixic Acid (8.53) at...

Since the use of human plasma as a model for skin esterases is debatable, the relevance of the biological results in Table 8.6 need validation as far as skin delivery is concerned. Indeed, permeation experiments across excised human skin showed that administration of prodrugs markedly improved the cutaneous delivery of nalidixic acid, with complete hydrolysis of the (acyl-oxy)methyl esters and significant, albeit incomplete, hydrolysis of the methyl and carbamoylmethyl esters [64],... 

H. Bundgaard, N. M0rk, A. Hoelgaard, Enhanced Delivery of Nalidixic Acid through Human Skin via Acyloxymethyl Ester Prodrugs , Int. J. Pharm. 1989, 55, 91-97. 

Fig. 7.12 Calixarene-based therapeutics anti-tubercular Macrocyclon [32] left) and a nalidixic acid delivering prodrug [34] (right)...

Diamba HM et al (2009) Towards calixarene-based prodrugs drug release and antibacterial behaviour of a water-soluble nalidixic acid/calix[4]arene ester adduct. Bioorg Med Chem Lett 19 2679-2682... 

---