A chlorodiazirine analog of pentamidine with anti-trypanosomal activity.
A chlorodiazirine derivative of pentamidine was synthesized and tested for anti-trypanosomal activity using EATRO stock 164 trypanosomes in cell culture. Anti-trypanosomal activity was measured as a decrease in [3H]hypoxanthine incorporation by the organisms. The derivative, 3,3'-[1,5-pentanediylbis(oxy-4,1-phenylene)]bis(3-chloro-3H-diazir ine), at a treatment level of 0.1 microM inhibited isotope incorporation by 40-50% compared to nontreated controls. At this concentration, pentamidine inhibited incorporation only 10-15%. The derivative is a nonionic molecule with much different solubility properties than the parent compound and should readily cross the blood-brain barrier.
Nichols
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Department of Chemistry, University of North Alabama, Florence 35632, USA.
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D000818:Animals; D001389:Azirines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D010419:Pentamidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014344:Trypanocidal Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
C404903:3,3'-(1,5-pentanediylbis(oxy-4,1-phenylene))bis(3-chloro-3H-diazirine); D001389:Azirines; D014344:Trypanocidal Agents; D010419:Pentamidine