Mechanism of action of cinodine, a glycocinnamoylspermidine antibiotic

The mechanism of action of cinodine, a glycocinnamoylspermidine antibiotic, was investigated. Upon addition of cinodine to growing cultures of Escherichia coli, a rapid decline in viable cell numbers was observed. Culture turbidity continued to increase for a short period before plateauing. Microscopic examination indicated that the antibiotic-treated cells continued to elongate with subsequent formation of serpentine-like structures. Radioisotopic-labeling studies of E. coli demonstrated that deoxyribonucleic acid (DNA) synthesis was immediately and irreversibly inhibited upon addition of cinodine. Ribonucleic acid synthesis was reduced after a significant delay, whereas protein synthesis remained unaffected. There was a minor degree of inhibition of incorporation of radiolabeled diaminopimelic acid into cell wall material. Cinodine likewise inhibited bacteriophage T7 DNA synthesis in infected E. coli cells. After inhibition of E. coli DNA synthesis by cinodine, intracellular DNA degradation was observed. Equilibrium dialysis studies demonstrated that the drug physically bound to DNA. These data indicate that cinodine functions as a potent irreversible inhibitor of bacterial and phage DNA synthesis.