Indirect inhibition by antibiotics of nucleotide and deoxynucleotide biosynthesis in Plasmodium falciparum.

ABSTRACT

The effects of the antibiotics, doxycycline, azithromycin, ciprofloxacin and chloramphenicol, upon levels of nucleoside-5'-triphosphates (NTPs) and 2'-deoxynucleoside-5'-triphosphates (dNTPs) have been compared in the malarial parasite, Plasmodium falciparum, and in human CCRF-CEM leukemia cells. All 4 antibiotics had more severe effects upon levels of NTPs and dNTPs in P. falciparum compared with leukemia cells providing an explanation for their selective toxicity against malaria and their utility as antimalarial drugs. In bacteria, the first 3 drugs inhibit protein synthesis while ciprofloxacin inhibits topoisomerase II. The observed depletions of NTPs and dNTPs would be a secondary effect of the drug but may result in death of the parasite.