Nitrobenzyl esters as potential conjugated alkylating and differentiation promoting agents: Antitumor effect in vivo

Article abstract of DOI:10.1016/0223-5234(90)90146-T

A series of ortho and para-nitrobenzyl esters of short chain fatty acids (C₂ to C₅) and of the lipophilic aminoacid, L-valine, and some other o-nitrobenzylated products were prepared. Bioreductive or hydrolytic cleavages of these compounds could release both differentiation promoting agents such as butyric acid and electrophilic moieties able to alkylate DNA. The antitumor effects of these compounds, either alone and/or associated with an immunostimulating agent (corynebacterium parvum, CP) or interferon (IFN) treatment, was studied using the 180 TG Crocker Sarcoma grafted onto Swiss mice. Based on the mean survival time and the final survival rate, the most active compounds used alone were the o-nitrobenzyl acetate and the 0-nitrobenzyl butyrate. Previous stimulation of the immune competent cells by CP before antitumor treatment increased the efficiency of most of the nitrobenzylated derivatives studied. The association with IFN did not significantly improve the antitumor effect.