Synthesis and study of the antischistosomal potency and induced biological parameters of a new 2-palmitoyl analogue of the universal antihelminthic praziquantel.
2-Palmitoyl[1,2,3,6,7,11b]hexahydro-4H-pyrazino[2-la]isoquinoline-4-one [III] a highly lipophilic analogue of the universal antihelminthic PRAZIQUANTEL [I] was rationally multi-stepwise synthesized and antischistosomally and biochemically screened. The 2-palmitoyl conjugation was hypothesized to be an antischistosomal adjuvant (Tween 40 mimicry), to the reported crucial pyrazino-isoquinoline moiety. On a constant weight doses bases of I and III (500 mg/kg mouse body weight), the activity of III was found to be approximately 70% of I (mice infected with S. mansoni cercariae) and with satisfactory toxicological and biochemical profile (mice liver and kidney functions). Equivalent molar weight assay (M 1:1.4 for I and III, respectively), which could further plead in favour of the potency of III, was not yet tested. The analogue III, which favourable incorporates the human metabolically and physiologically compatible, palmitic acid segment, seems to be an antischistosomally promising candidate for more integrated studies.
Abo-Ghalia
M H
MH
National Research Centre, Dokki, Cairo, Egypt.
Soliman
A M
AM
D000818:Animals; D051379:Mice; D010168:Palmitates / Q000138:chemical synthesis / Q000494:pharmacology; D011223:Praziquantel / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D012550:Schistosoma mansoni / Q000187:drug effects; D012555:Schistosomiasis mansoni / Q000097:blood / Q000188:drug therapy; D012556:Schistosomicides / Q000138:chemical synthesis* / Q000494:pharmacology
D010168:Palmitates; D012556:Schistosomicides; D011223:Praziquantel