title: Synthesis of novel hybrid molecules from precursors with known antiparasitic activity.
abstract: Three novel new compounds derived from antiparasitic precursors have been synthesized and tested for their antiamoebic and antigiardial activities. The condensation of 2-(2-methyl-5-1H-nitroimidazolyl)ethylamine (6) with 5-nitro-2-furylacrylic acid (7) gave 3-(5-nitrofuran-2-yl)-N-[2-(5-nitroimidazol-1-yl)ethyl]acrylamide (8). Condensation of 7 with 7-chloro-4-(piperazin-1-yl)quinoline (9) afforded 1-[4-(7-chloroquinolin-4-yl)piperazin-1-yl)-3-(5-nitrofuran-2-yl)propenone as a mixture of two isomers; 10-a (the E-isomer) and 10-b (the Z-isomer). In addition, the reaction of 9 with 1-(2-bromoethyl)-2-methyl-5-nitroimidazole (11) in the presence of K(2)CO(3) and NaI yielded 7-chloro-4-(4-[2-(5-nitroimidazol-1-yl)ethyl]-piprazin-1-yl)quinoline (12). On the basis of preliminary screening data for these new compounds, compound 12 exhibited potent lethal activities against Entamoeba histolytica and Giardia intestinalis; its IC(50) (about 1 microM) was lower, at least by a factor of five, compared to the standard drug, metronidazole. In addition, the IC(50) of compound 12 against the tested parasites is 600 times below that against Hep-2 and Vero cells. Compounds 8 and 10-a also exhibited potent or moderate antiamoebic and antigiardial activities with IC(50 values) of about 5.5 microM, and 140 microM, respectively, against the tested parasites. These two hybrid molecules, 8, 10-a, were also non-cytotoxic at the lethal concentrations against the parasites.
authors.affiliation: Chemistry Department, Faculty of Science, University of Jordan, Amman 11942, Jordan. h.saadeh@ju.edu.jo
authors.forename: Haythem A
authors.initials: HA
authors.lastname: Saadeh
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: Mosleh
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Mubarak
mesh_terms: D000178:Acrylamides / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D000977:Antiparasitic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004748:Entamoeba histolytica / Q000187:drug effects*; D016829:Giardia lamblia / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D009581:Nitrofurans / Q000138:chemical synthesis / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D000178:Acrylamides; D000977:Antiparasitic Agents; D009581:Nitrofurans; D011804:Quinolines