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Herbicide and Pharmaceutical Relationships

Published online by Cambridge University Press:  20 January 2017

Stephen O. Duke*
Affiliation:
Natural Products Utilization Research Unit, Agricultural Research Service, U.S. Department of Agriculture, P.O. Box 8048, University, MS 38677
*
Corresponding author's E-mail: [email protected]

Abstract

For many years, virtually all pharmaceutical companies had an agrochemical division. This was partly to maximize the benefits of expensive chemical synthesis efforts by searching for many types of useful biological activities. Leads for pharmaceuticals and pesticides often overlap, in some cases leading to similar compounds used for human health and weed management purposes. This review will focus on herbicides and herbicide classes that have potential pharmaceutical properties, both as therapeutic agents that act through human molecular target sites and those that act on infectious agents. An example of the first case is compounds that target plant acetyl coenzyme A carboxylases, inhibiting fatty acid synthesis, and similar compounds used in humans as anti-inflammatory agents. Another such example is the triketone class of compounds that can act both as herbicides and as treatments for the genetic disease tyrosinemia, targeting the same enzyme in both cases. Examples of the second case are the relatively large number of herbicides that have activity against the malaria protozoan (Plasmodium spp.). It turns out that Plasmodium spp. and related disease organisms have an organelle that is apparently analogous to the plant plastid, the apicoplast. Herbicides such as dinitroanilines are active against several protozoan parasites by the same mechanism by which they kill plants, interaction with tubulin to halt cell division and other tubulin-dependent processes. These and other multiple activities of various herbicides and herbicide classes provide perspective on the broad biological activity of herbicides and related compounds.

Type
Symposium
Copyright
Copyright © Weed Science Society of America 

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References

Literature Cited

Al-Dhalimy, M., Overturf, K., Finegold, M., and Grompe, M. 2002. Long-term therapy with NTBC and tyrosine-restricted diet in a murine model of hereditary tyrosinemia type I. Mol. Genet. Metab. 75:3845.Google Scholar
Ayaydin, F., Vissi, E., Mészáros, T., et al. 2000. Inhibition of serine/threonine-specific protein phosphatases causes premature activation of cdc2MsF kinase at G2/M transition and early mitotic microtubule organisation in alfalfa. Plant J. 23:8596.Google Scholar
Bajsa, J., Duke, S. O., and Tekwani, B. L. 2008. Plasmodium falciparum serine/threonine phosphoprotein phosphatases (PPP): from housekeeper to the ‘Holy Grail’. Curr. Drug Targets. 9:9971012.Google Scholar
Bajsa, J., Singh, K., Nanayakkara, D., Duke, S. O., Rimando, A. M., Evidente, A., and Tekwani, B. L. 2007. A survey of synthetic and natural phytotoxic compounds and phytoalexins as potential antimalarial compounds. Biol. Pharm. Bull. 30:17401744.Google Scholar
Bell, A. 1998. Microtubule inhibitors as potential antimalarial agents. Parasitol. Today. 14:234240.Google Scholar
Benbow, J. W., Korda, A., and Mead, J. R. 1998. Synthesis and evaluation of dinitroanilines for treatment of cryptoporidiosis. Antimicrob. Agents Chemother. 442:339343.Google Scholar
Brown, G. M. 1962. The biosynthesis of folic acid. II. Inhibition by sulfonamides. J. Biol. Chem. 237:536540.Google Scholar
Burnier, M. and Brunner, H. 2000. Angiotensin II receptor antagonists. The Lancet. 355:637645.Google Scholar
Campbell, M., Anderson, P., and Trimble, E. R. 2008. Glucose lowers the threshold for human aortic vascular smooth muscle cell migration: inhibition by protein phosphatase-2A. Diabetologia. 51:10681080.Google Scholar
Chan, M. M. and Fong, D. 1990. Inhibition of leishmanias but not host macrophages by the antitubulin herbicide trifluralin. Science. 249:924926.Google Scholar
Chan, M. M., Grogli, M., Chen, C-C., Bienens, E. J., and Fong, D. 1993. Herbicides to curb human parasitic infections: in vitro and in vivo effects of trifluralin on the trypanosomatid protozoans. Proc. Natl. Acad. Sci. USA. 90:56575661.Google Scholar
d'Atri, G., Gomarasca, P., Resnati, G., Tronconi, G., Scolastico, C., and Sirtori, C. R. 1984. Novel pyrimidine and 1,3,5-triazine hypolipidemic agents. J. Med. Chem. 27:16211629.Google Scholar
Dayan, F. E. and Duke, S. O. 2003. Herbicides: Protoporphyrinogen oxidase inhibitors. Pages 850863. in Plimmer, J. R., Gammon, D. W., and Ragsdale, N. N. eds. Encyclopedia of Agrochemicals. Vol. 2. New York: John Wiley & Sons.Google Scholar
Delaney, J., Clarke, E., Hughes, D., and Rice, M. 2006. Modern agrochemical research: a missed opportunity for drug discovery. Drug Discov. Today. 11:839845.Google Scholar
Diacovich, L., Michell, D. L., Pham, H., Gago, G., Melgar, M. M., Khosla, C., Gramajo, H., and Tsai, S-C. 2004. Crystal structure of the β-subunit of acyl-CoA carboxylase: structure-based engineering of substrate specificity. Biochemistry. 43:14,02714,036.Google Scholar
Fast, N. M., Kissinger, J. C., Roos, D. S., and Keeling, P. J. 2001. Nuclear-encoded, plastid-targeted genes suggest a single common origin for apicomplexan and dinoflagellate plastids. Mol. Biol. Evol. 18:418426.Google Scholar
Fennell, B. J., Naughton, J. A., Brennan, G., Fairweather, I., Hoey, E., McFerran, N., Trudgett, A., and Bell, A. 2008. Microtubules as antiparasitic drug targets. Expert Opin. Drug Discov. 3:501518.Google Scholar
Fennell, B. J., Naughton, J. A., Dempsey, E., and Bell, A. 2006. Cellular and molecular actions of dinitroaniline and phosphorothioamidate herbicides on Plasmodium falciparum: tubulin as a specific antimalarial target. Mol. Biochem. Parasitol. 145:226238.Google Scholar
Fingar, V. H., Wieman, T. J., Mcmahon, K. S., Haydon, P. S., Halling, B. P., Yuhas, D. A., and Winkelman, J. W. 1997. Photodynamic therapy using a protoporphyrinogen oxidase inhibitor. Cancer Res. 57:45514556.Google Scholar
Haselkorn, R. and Gornicki, P. 2006. cDNAs for human acetyl-CoA carboxylase and their use in screening for effectors of the enzyme for therapeutic use. Patent PCT Int. 159. CODEN: PIXXD2 WO 2006130470 A2 20061207 CAN 146:39775 AN 2006:1285827.Google Scholar
Jelenska, J., Crawford, M. J., Harb, O. S., Zuther, E., Haselkorn, R., Roos, D. S., and Gornicki, P. 2001. Subcellular localization of acetyl-CoA carboxylase in the apicomplexan parasite Toxoplasma gondii . Proc. Natl. Acad. Sci. USA. 98:27232728.Google Scholar
Kaidoh, T., Fujioka, H., Okoye, V., and Aikawa, M. 1995. Effect and localization of trifluralin in Plasmodium flaciparum gametocytes: an electron microscopy study. J. Euk. Microbiol. 42:6164.Google Scholar
Kemal, C. and Casida, J. E. 1992. Coenzyme A esters of 2-aryloxyphenoxypropionate herbicides and 2-arylpropionate antiinflammatory drugs are potent and stereoselective inhibitors of rat liver acetyl-CoA carboxylase. Life Sci. 50:533540.Google Scholar
Kirchengast, M. and Muenter, K. 1999. Multicomponent pharmaceutical formulations for treatment of vasoconstrictive disorders. Ger. Offen. (1999). 34. CODEN: GWXXBX DE 19743143 A1 19990401 Patent written in German. Application: DE 97-19743143 19970930. Priority: CAN 130:257367 AN 1999:234126.Google Scholar
Li, Y. and Casida, J. 1992. Cantharidin-binding protein: identification as protein phosphatase 2A. Proc. Natl. Acad. Sci. USA. 89:11,86711,870.Google Scholar
Lichtenthaler, H. K., Zeidler, J., Schwender, J., and Muller, C. 2000. The nonmevalonate isoprenoid biosynthesis of plants as a test system for new herbicides and drugs against pathogenic bacteria and the malaria parasite. Z. Naturforsch. 55C:305313.Google Scholar
Lipinski, C. A., Lombardo, F., Dominy, B. W., and Feeney, P. J. 1997. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 23:325.Google Scholar
Liu, D. and Chen, Z. 2009. The effects of cantharidin and cantharidin derivative on tumour cells. Anti-Cancer Med. Chem. 9:392396.Google Scholar
Mandal, S. B., Sahabuddin, S. K., Singha, K., Roy, A., Roy, B. G., Maity, J. K., and Achari, B. 2005. Recent synthetic forays into carbocyclic as well as spirocyclic nucleosides and analogs from carbohydrate derived precursors. Proc. Indian Natl. Sci. Acad. Part A Phys. Sci. 71:283307.Google Scholar
March, L. C., Bajwa, G. S., Lee, J., Wasti, K., and Joulie, M. M. 1976. Antimalarials. 3. 1,2,4-triazines. J. Med. Chem. 19:845848.Google Scholar
Moreau, D., Jacquot, C., Tsita, P., Chinou, I., Tomasoni, C., and Juge, M. 2008. Original triazine inductor of new specific molecular targets, with antitumor activity against nonsmall cell lung cancer. Int. J. Cancer. 123:26762683.Google Scholar
Morré, D. J. and Reust, T. 1997. A circulating form of NADH oxidase activity responsive to the antitumor sulfonylurea N-4-(methylphenylsulfonyl)-N′-(4-chlorophenyl)urea (LY181984) specific to sera from cancer patients. J. Bioenerg. Biomembr. 29:281289.Google Scholar
Mueller, C., Schwender, J., Zeidler, J., and Lichtenthaler, H. K. 2000. Properties and inhibition of the first two enzymes of the non-mevalonate pathway of isoprenoid bioynthesis. Biochem. Soc. Trans. 28:792793.Google Scholar
Nakashima, M., Uematsu, T., Takiguchi, Y., and Hayashi, T. 1984. Phase I study of 2,4-diamino-6-(2,5-dichlorophenyl)-s-triazine maleate (MN-1695), a new anti-ulcer agent. Arzneimittel-Forschung. 34:492498.Google Scholar
Nettleton, M. J., Poyser, R. H., and Shorter, J. H. 1974. Cardiovascular effects of two new triazine antimalarials, BRL 50216 (clociguanil) and BRL 6231. Toxicol. Appl. Pharmacol. 27:271282.Google Scholar
Roberts, C. W., Roberts, F., Lyons, R. E., et al. 2002. The shikimate pathway and its branches in apicomplexan parasites. J. Infect. Dis. 185 (Suppl):S25S36.Google Scholar
Roberts, F., Roberts, C. W., Johnson, J. J., et al. 1998. Evidence for the shikimate pathway in apicomplexan parasites. Nature. 393:801805.Google Scholar
Rodriguez-Concepcion, M. 2004. The MEP pathway: a new target for the development of herbicides, antibiotics and antimalarial drugs. Curr. Pharm. Design. 10:23912400.Google Scholar
Saczewski, F. and Bulakowska, A. 2006. Synthesis, structure and anticancer activity of novel alkenyl-1,3,5-triazine derivatives. Eur. J. Med. Chem. 41:611615.Google Scholar
Sano, H., Mio, S., Hamura, M., Kitagawa, J., Shindou, M., Honma, T., and Sugai, S. 1995. Synthesis and herbicidal activity of hydantocidin analogs: modification of the carbonyl groups in spirohydantoin. Biosci. Biotechnol. Biochem. 59:22472250.Google Scholar
Schobert, R., Biersack, B., Knauer, S., and Ocker, M. 2008. Conjugates of the fungal cytotoxin illudin M with improved tumor specificity. Bioorg. Med. Chem. 16:85928597.Google Scholar
Shah, M. H., Deliwala, V. C., and Sheth, U. K. 1968. Synthesis and diuretic activity of 2-amino-4-arylamino-6-mercapto-s-triazines and related derivatives. J. Med. Chem. 11:11671171.Google Scholar
Shaner, D. L. 2004. Herbicide safety relative to common targets in plants and mammals. Pest Manag. Sci. 60:1724.Google Scholar
Singh, N., Chevé, G., Avery, M. A., and McCurdy, C. R. 2007. Targeting the methyl erythritol phosphate (MEP) pathway for novel antimalarial, antibacterial and herbicidal drug discovery: inhibition of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) enzyme. Curr. Pharm. Design. 13:11611177.Google Scholar
Stokkermans, T. J. W., Schartzman, J. D., Keenan, K., Morrissette, N. S., Tilney, L. G., and Roos, D. S. 1996. Inhibition of Toxaplasm gondii replication by dinitroaniline herbicides. Exp. Parasitol. 84:355370.Google Scholar
Sung, T. W., Skillman, T. R., Yang, N., and Hammond, C. 2003. Cyclohexanedione herbicides are inhibitors of rat heart acetyl-CoA carboxylase. Bioorg. Med. Chem. Lett. 13:32373242.Google Scholar
Taha, M. O., Dahabiyeh, L. A., Bustanji, Y., Zalloum, H., and Saleh, S. 2008. Combining ligand-based pharmacophore modeling, quantitative structure-activity relationship analysis and in silico screening for the discovery of new potent hormone sensitive lipase inhibitors. J. Med. Chem. 51:64786494.Google Scholar
Testa, C. A. and Brown, M. J. 2003. The methylerythritol phosphate pathway and its significance as a novel drug target. Curr. Pharm. Biotech. 4:248259.Google Scholar
Thiery, J. P., Blazsek, I., Legras, S., Marion, S., Reynes, M., Anjo, A., Adam, R., and Misset, J. L. 1999. Hepatocellular carcinoma cell lines from diethylnitrosamine phenobarbital-treated rats. Characterization and sensitivity to endothall, a protein serine/threonine phosphatase 2A inhibitor. Hepatology. 29:14061417.Google Scholar
Tice, C. M. 2001. Selecting the right compounds for screening: does Lipinski's rule of 5 for pharmaceuticals apply to agrochemicals? Pest Manag. Sci. 57:316.Google Scholar
Traub-Cseko, Y. M., Ramalho-Ortigão, J. M., Dantas, A. P., de Castro, S. L., Barbosa, H. S., and Downing, K. H. 2001. Dinitroaniline herbicides against protozoan parasites: the case of Trypanosoma cruzi . Trends Parasitol. 17:136141.Google Scholar
Travis, K. Z. and Posner, J. 2008. HPPD inhibitors in the treatment of depression and/or withdrawal symptoms associated with additive drugs. PCT Int. Appl. PCT/GB2006/003099, Publication WO/2008/020150. 45.Google Scholar
Turner, R. C., Cull, C. A., Frighi, V., and Holman, R. R. 1999. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus. JAMA. 281:20052012.Google Scholar
Veerasekaran, P., Kirkwood, R. C., and Parnell, E. W. 1981. Studies of the mechanism of action of asulam in plants. II. Effect of asulam on the biosynthesis of folic acid. Pestic. Sci. 12:330338.Google Scholar
Vu, C. B., Pan, D., Peng, B., et al. 2005. Novel diamino derivatives of [1,2,4]triazolo[1,5-a][1,3,5] triazine as potent and selective adenosine A2a receptor antagonists. J. Med. Chem. 48:20092018.Google Scholar
Wilson, R. J. M., Rangachari, K., Saldanha, J. W., Rickman, L., Buxton, R. S., and Eccleston, J. F. 2003. Parasite plastids: maintenance and functions. Phil. Trans. R. Soc. London B. 358:155164.Google Scholar
Zohar, Y., Einav, M., Chipman, D. M., and Barak, Z. 2003. Acetohydroxyacid synthase from Mycobacterium avium and its inhibition by sulfonylureas and imidazolinones. Biophys. Biophys. Acta. 1649:97105.Google Scholar
Zuther, E., Johnsson, J. J., Haselkorn, R., and McLeod, R. 1999. Growth of Toxoplasma gondii is inhibited by aryloxyphenoxypropionate herbicides targeting acetyl-CoA carboxylase. Proc. Natl. Acad. Sci. USA. 96:13,38713,392.Google Scholar