Synthesis and evaluation of dinitroanilines for treatment of cryptosporidiosis.

Antimicrobial Agents and Chemotherapy
J W BenbowJ R Mead

Abstract

The efficacy of a series of dinitroaniline herbicide derivatives for the treatment of Cryptosporidium parvum infections has been studied. The lead compounds oryzalin (compound 1) and trifluralin (compound 2) have low water solubility (<3 ppm) which was alleged to be a major contributor to their poor pharmacokinetic availability. Derivatives of compounds 1 and 2 were synthesized. In these derivatives the functionality at the C-1 amine position or the C-4 position was substituted with groups with various hydrophilicities to determine if a direct relation existed between water solubility and overall activity. The chlorinated precursors of these derivatives were also examined and were found to be less active in the C. parvum assays, a result in direct contrast to earlier work with Leishmania. Enhanced water solubility alone did not overcome the drug availability problem; however, several candidates with similar activities but with toxicities lower than those of the lead compounds were produced.

References

Mar 1, 1992·Mayo Clinic Proceedings·J E Rosenblatt
Jun 1, 1991·The Journal of Infectious Diseases·J E Rehg
Nov 1, 1994·Experimental Parasitology·N S MorrissetteD S Roos
Feb 1, 1995·International Journal for Parasitology·P J O'Donoghue
Sep 1, 1994·Antiviral Research·M S Belen'kii, R F Schinazi
Apr 1, 1993·Antimicrobial Agents and Chemotherapy·P BrasseurJ J Ballet
Jun 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·M M ChanD Fong
Mar 1, 1996·FEMS Microbiology Letters·M J ArrowoodX You

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Citations

Jul 20, 2002·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Jan R Mead
Aug 6, 2002·Bioorganic & Medicinal Chemistry Letters·Gautam BhattacharyaKarl A Werbovetz
Jun 27, 2007·Parasitology Research·Annunziata GiangasperoOlga Brandonisio
Aug 9, 2007·Future Microbiology·Barbara Kappes, Petra Rohrbach
Feb 15, 2002·Bioorganic & Medicinal Chemistry Letters·Esther del OlmoArturo San Feliciano
Mar 5, 2002·Microbiology and Molecular Biology Reviews : MMBR·Naomi S Morrissette, L David Sibley
Oct 25, 2011·Eukaryotic Cell·Johnson Q TranNaomi S Morrissette
Feb 11, 2010·Antimicrobial Agents and Chemotherapy·Christopher MaNaomi Morrissette
Jan 23, 2004·The Journal of Eukaryotic Microbiology·Jan R MeadNina McNair
Apr 21, 2010·Parasitology Research·Letícia L TerraWanderley De Souza
Nov 6, 2020·Rapid Communications in Mass Spectrometry : RCM·Diego D ColasurdoDanila L Ruiz
Apr 5, 2001·Trends in Parasitology·Y M Traub-CsekoK H Downing
Jul 1, 2004·Bioorganic & Medicinal Chemistry Letters·Neetu TewariSuman Gupta
May 6, 2006·Bioorganic & Medicinal Chemistry·Tesmol G GeorgeKarl A Werbovetz
Sep 26, 2014·Chemical Reviews·Hidayat HussainSimon Gibbons
Aug 3, 2010·Bioorganic & Medicinal Chemistry Letters·Molla M EndeshawKarl A Werbovetz

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