Synthesis of novel hybrid molecules from precursors with known antiparasitic activity

Haythem A. Saadeh, Ibrahim M. Mosleh, Mohammad S. Mubarak

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

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 2CO3 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 IC50 ( about 1 μM) was lower, at least by a factor of five, compared to the standard drug, metronidazole. In addition, the IC50 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 IC50 values of about 5.5 μM, and 140 μM, respectively, against the tested parasites. These two hybrid molecules, 8, 10-a, were also non-cytotoxic at the lethal concentrations against the parasites.

Original languageEnglish
Pages (from-to)1483-1494
Number of pages12
JournalMolecules
Volume14
Issue number4
DOIs
Publication statusPublished - Apr 2009
Externally publishedYes

Keywords

  • Chloroquine
  • Entamoeba Histolytica
  • Giardia Intestinalis
  • Hybrid Molecules
  • Metronidazole

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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