Synthesis and evaluation of antiparasitic activities of new 4-[5-(4-phenoxyphenyl)-2H-pyrazol-3-yl]morpholine derivatives.
A series of new 4-[5-(4-phenoxyphenyl)-2H-pyrazol-3-yl]morpholine derivatives, prepared by two synthetic routes, were in vitro assayed against three Trypanosoma strains, Leishmania donovani, and Plasmodium falciparum K1. Seven out of 17 compounds showed moderate to very good activity against blood stage T. b. rhodesiense, with 10 and 17 exhibiting highest potency (IC50 of 1.0 and 1.1 microM, respectively). Interestingly, the beta-diketone precursors 1-3 had good antitrypanosomal activity toward the insect stage, with IC50 values of 1.0-3.4 microM. Among different compounds with moderate activity against T. cruzi, compound 17 showed the lowest IC50 value of 9.5 microM; thus, the series seemed to act selectively toward the different Trypanosoma parasites. Eight compounds were moderately active against L. donovani, with 2, 3, and 12 being the most promising ones (IC50 values of 2.3-5.2 microM), whereas compound 14 was the only derivative with good activity against P. falciparum (IC50 of 3.7 microM).
Kuettel
Sabine
S
Pharmaceutical Biochemistry Group, School of Pharmaceutical Sciences, University of Geneva, Quai Ernest-Ansermet 30, CH-1211 Geneva 4, Switzerland.
Zambon
Alfonso
A
Kaiser
Marcel
M
Brun
Reto
R
Scapozza
Leonardo
L
Perozzo
Remo
R
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007893:Leishmania donovani / Q000187:drug effects; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014345:Trypanosoma / Q000187:drug effects
D000962:Antimalarials; D009025:Morpholines; D011720:Pyrazoles; D014344:Trypanocidal Agents