RESUMO
Two eudesmanes, two abietanes, two podocarpanes and other nine known compounds were isolated from the dried fruits of Juniperus polycarpus var. seravschanica. Their structures were established on the basis of analysis of spectroscopic evidence. Some of the isolated terpenoids showed antimalarial activity.
Assuntos
Juniperus/química , Terpenos/análise , Abietanos/análise , Abietanos/química , Abietanos/farmacologia , Animais , Antimaláricos/análise , Antimaláricos/química , Antimaláricos/farmacologia , Diterpenos/análise , Diterpenos/química , Diterpenos/farmacologia , Frutas/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/análise , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/crescimento & desenvolvimento , Sesquiterpenos/análise , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos de Eudesmano/análise , Sesquiterpenos de Eudesmano/química , Sesquiterpenos de Eudesmano/farmacologia , Terpenos/química , Terpenos/farmacologiaRESUMO
Tetra-acetamide pyrroloquinazolinediamine (PQD-A4) and bis-ethylcarbamyl pyrroloquinazolinediamine (PQD-BE) are new derivatives of pyrroloquinazolinediamine (PQD) and are being investigated as potential chemotherapeutic agents for the treatment of malaria. Comparative studies to assess the therapeutic indices of PQD-A4, PQD-BE, and PQD were conducted in Plasmodium berghei-infected rats following daily intragastric dosing for three consecutive days. Artesunate (AS), a standard drug for treatment of severe malaria, was used as a comparator. The minimum doses required to clear malaria parasitemia were 156 micromol/kg of body weight for AS and 2.4 micromol/kg for PQD, PQD-4A, and PQD-BE. The maximum tolerated dose (MTD) of AS was 625 micromol/kg, and its therapeutic index was calculated to be 4. The MTDs of PQD-A4, PQD-BE, and PQD were found to be 190, 77, and 24 micromol/kg, respectively, yielding therapeutic indices of 80, 32, and 10, respectively. Although PQD-A4 and PQD-BE are only half as potent as PQD based on their curative effects, the two new derivatives, PQD-4A and PQD-BE, are 8.0-fold and 3.2-fold safer, respectively, than their parent compound when they are dosed for three consecutive days. Oral PQD-A4 and PQD-BE are 44 to 70 times more potent on an mg basis than intravenous AS. As assessed from the therapeutic index over 3 days, PQD-A4, PQD-BE, and PQD administered orally are 20.0, 8.0, and 2.5 times safer than AS given intravenously. The results indicate that PQD-4A is a promising candidate for antimalarial treatment.