Synthesis of novel hybrid molecules from precursors with known antiparasitic activity.
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.
Saadeh
Haythem A
HA
Chemistry Department, Faculty of Science, University of Jordan, Amman 11942, Jordan. h.saadeh@ju.edu.jo
Mosleh
Ibrahim M
IM
Mubarak
Mohammad S
MS
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
D000178:Acrylamides; D000977:Antiparasitic Agents; D009581:Nitrofurans; D011804:Quinolines