In vitro anticryptosporidial activity of dinitroaniline herbicides

Arrowood, Michael J.; Mead, Jan R.; Xie, Long-Ti; You, Xiangdong

doi:10.1016/0378-1097(96)00003-1

Cited by 12 publications

(14 citation statements)

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“…Dinitroanilines, including trifluralin, are herbicides that block microtubule formation and inhibit cryptosporidial growth in vitro and in vivo. 84–86 Furthermore, the development of hybrid compounds based on albendazole and trifluralin led to the identification of analogues with excellent in-vitro efficacy and 79–81% reductions in oocyst shedding in mice (Thompson RCA, unpublished).…”

Section: Therapeuticsmentioning

confidence: 99%

A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium

Checkley

White

Jaganath

et al. 2015

The Lancet Infectious Diseases

803

703

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Cryptosporidium spp are well recognised as causes of diarrhoeal disease during waterborne epidemics and in immunocompromised hosts. Studies have also drawn attention to an underestimated global burden and suggest major gaps in optimum diagnosis, treatment, and immunisation. Cryptosporidiosis is increasingly identified as an important cause of morbidity and mortality worldwide. Studies in low-resource settings and high-income countries have confirmed the importance of cryptosporidium as a cause of diarrhoea and childhood malnutrition. Diagnostic tests for cryptosporidium infection are suboptimum, necessitating specialised tests that are often insensitive. Antigen-detection and PCR improve sensitivity, and multiplexed antigen detection and molecular assays are underused. Therapy has some effect in healthy hosts and no proven efficacy in patients with AIDS. Use of cryptosporidium genomes has helped to identify promising therapeutic targets, and drugs are in development, but methods to assess the efficacy in vitro and in animals are not well standardised. Partial immunity after exposure suggests the potential for successful vaccines, and several are in development; however, surrogates of protection are not well defined. Improved methods for propagation and genetic manipulation of the organism would be significant advances.

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Section: Therapeuticsmentioning

confidence: 99%

A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium

Checkley

White

Jaganath

et al. 2015

The Lancet Infectious Diseases

803

703

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“…They are herbicidal because they disrupt microtubules and, therefore, cell division (Parka and Soper 1977;Corbett et al 1984). In recent years, evidence has accumulated that these drugs are eective against certain parasitic protozoa, including Leishmania species (Chan and Fong 1990;Chan et al 1991Chan et al , 1993, Trypanosoma brucei (Chan et al 1993), Plasmodium falciparum (Nath and Schneider 1992), Toxoplasma gondii (Stokkermans et al 1996), and Cryptosporidium parvum (Arrowood et al 1996). Therefore, we have examined the eect of these dinitroanilines on the growth of Entamoeba histolytica and E. invadens and have demonstrated inhibition of the growth of both amebas by these dinitroanilines, whereby oryzalin was much more eective than tri¯uralin and E. invadens was more resistant to these drugs than was E. histolytica (Makioka et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Effect of the antitubulin drug oryzalin on the encystation of Entamoeba invadens

Makioka¹,

Kumagai²,

Ohtomo³

et al. 2000

Parasitol Res

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We have recently demonstrated that the antimicrotubule drug oryzalin inhibits the growth of Entamoeba invadens as well as E. histolytica, the former being more resistant to the drug than the latter, and that effective doses of oryzalin are higher for Entamoeba than for the other parasitic protozoa examined thus far. The aim of the present study was to examine the effect of oryzalin on the encystation of E. invadens using an axenic encystation system in vitro. Oryzalin inhibited the encystation of E. invadens strain IP-1 in a dose-dependent manner. The addition of oryzalin after the induction of encystation was also inhibitory for encystation and cyst maturation. Trophozoites incubated for 1 day in encystation medium with oryzalin did not encyst after removal of the drug. Although trophozoites grown in the presence of 300 microM oryzalin for 2 days did not encyst after their transfer to encystation medium containing the same concentration of drug, a number of trophozoites survived for at least 3 days. In contrast, trophozoites grown in the absence of oryzalin neither survived nor encysted after their transfer to encystation medium supplemented with the drug, which suggests that pretreatment of trophozoites with oryzalin contributes to their continued survival as trophozoites, i.e., without their transforming into cysts, in encystation medium. Trophozoites grown with oryzalin did encyst after their transfer to encystation medium without the drug. Accumulation of trophozoites in the mitotic phase was observed after culture with oryzalin. When cysts prepared at day 1 of encystation, most of which were mononucleate, were reincubated in the presence of oryzalin for an additional 2 days, inhibition of their maturation was observed. Thus, oryzalin is a potent mitotic-phase inhibitor of E. invadens and may become a useful tool for studies on the relationship between the cell cycle and encystation of this parasite.

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“…1) were selective toward Leishmania (6)(7)(8) and Trypanosoma parasites (9) in mammalian hosts provided an exciting breakthrough for parasitic chemotherapy; selective eradication of the parasitic organism occurred with minimal damage to the host. Useful levels of activity against other apicomplexan parasites with negligible toxicity to the mammalian host have also been seen with these agents (1,12,16).…”

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confidence: 99%

Synthesis and Evaluation of Dinitroanilines for Treatment of Cryptosporidiosis

Benbow

Bernberg

Korda

et al. 1998

Antimicrob Agents Chemother

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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.

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In vitro anticryptosporidial activity of dinitroaniline herbicides

Cited by 12 publications

References 0 publications

A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium

A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium

Effect of the antitubulin drug oryzalin on the encystation of Entamoeba invadens

Synthesis and Evaluation of Dinitroanilines for Treatment of Cryptosporidiosis

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