Antituberculotic and antiprotozoal activities of primin, a natural benzoquinone: in vitro and in vivo studies.
Primin (=2-methoxy-6-pentylcyclohexa-2,5-diene-1,4-dione), a natural benzoquinone synthesized in our laboratory, was investigated for its in vitro antiprotozoal, antimycobacterial, and cytotoxic potential. Primin showed very potent activity against Trypanosoma brucei rhodesiense (IC50 0.144 microM) and Leishmania donovani (IC50 0.711 microM), and revealed low cytotoxicity (IC50 15.4 microM) on mammalian cells. Only moderate inhibitory activity was observed against Mycobacterium tuberculosis, Trypanosoma cruzi, and Plasmodium falciparum. When tested for in vivo efficacy in a Trypanosoma b. brucei rodent model, primin failed to cure the infection at 20 mg/kg given intraperitoneally. Primin was too toxic in vivo at a higher concentration (30 mg/kg, injected i.p. route) in mice infected with L. donovani. Taken together, primin can serve as a lead compound for the rational design of more potent and less toxic antiprotozoal agents.
Tasdemir
Deniz
D
Centre for Pharmacognosy and Phytotherapy, School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK. deniz.tasdemir@pharmacy.ac.uk
Brun
Reto
R
Yardley
Vanessa
V
Franzblau
Scott G
SG
Rüedi
Peter
P
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D016227:Benzoquinones / Q000138:chemical synthesis / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004912:Erythrocytes / Q000382:microbiology / Q000469:parasitology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D021261:Parasitic Sensitivity Tests
D000981:Antiprotozoal Agents; D000995:Antitubercular Agents; D016227:Benzoquinones; C004532:quinone; C014773:primin