Bahadur et al.
18. Valdez CA, Tripp JC, Miyamoto Y, Kalisiak J, Hruz P, Andersen YS,
Brown SE, Kangas K, Arzu LV, Davids BJ, Gillin FD, Upcroft JA,
Upcroft P, Fokin VV, Smith DK, Sharpless KB, Eckmann L. 2009.
Synthesis and electrochemistry of 2-ethenyl and 2-ethanyl derivatives of
5-nitroimidazole and antimicrobial activity against Giardia lamblia. J.
19. Irfan I, Sawangjaroen N, Bhat AR, Azam A. 2010. New dioxazole
derivatives: synthesis and effects on the growth of Entamoeba histolytica
and Giardia intestinalis. Eur. J. Med. Chem. 45:1648–1653. http://dx.doi
20. Chen CZ, Kulakova L, Southall N, Marugan JJ, Galkin A, Austin CP,
Herzberg O, Zheng W. 2011. High-throughput Giardia lamblia viability
assay using bioluminescent ATP content measurements. Antimicrob. Agents
21. Nillius D, Müller J, Müller N. 2011. Nitroreductase (GlNR1) increases
susceptibility of Giardia lamblia and Escherichia coli to nitro drugs. J.
presence or absence of O2 is a crucial variable that should be taken
into account when testing new potential drugs against Giardia.
ACKNOWLEDGMENTS
This work was partially supported by Ministero dell’Istruzione,
dell’Università e della Ricerca of Italy (FIRB RBFR08F41U_001 A.G.,
FIRB RBIN06E9Z8, and PRIN 20107Z8XBW_005 to P.S.); the Ministry of
Science & Technology, Department of Science & Technology (DST/INT/
UKR/2012/P-10), India; and the University of Delhi under the Strength-
ening R&D Doctoral Research Programme, Delhi, India.
REFERENCES
1. Ankarklev J, Jerlstrom-Hultqvist J, Ringqvist E, Troell K, Svard SG.
2010. Behind the smile: cell biology and disease mechanisms of Giardia
2. Adam RD. 2001. Biology of Giardia lamblia. Clin. Microbiol. Rev. 14:
22. Hounkong K, Sawangjaroen N, Phongpaichit S. 2011. A colorimetric
method for the evaluation of anti-giardial drugs in vitro. Exp. Parasitol.
23. Tejman-Yarden N, Miyamoto Y, Leitsch D, Santini J, Debnath A, Gut
J, McKerrow JH, Reed SL, Eckmann L. 2013. A reprofiled drug, aura-
nofin, is effective against metronidazole-resistant Giardia lamblia. Anti-
24. Müller J, Schildknecht P, Müller N. 2013. Metabolism of nitro drugs
metronidazole and nitazoxanide in Giardia lamblia: characterization of a
novel nitroreductase (GlNR2). J. Antimicrob. Chemother. 68:1781–1789.
25. Hayat F, Moseley E, Salahuddin A, Van Zyl RL, Azam A. 2011. Anti-
protozoal activity of chloroquinoline based chalcones. Eur. J. Med. Chem.
26. Dao TT, Nguyen PH, Lee HS, Kim E, Park J, Lim SI, Oh WK. 2011.
Chalcones as novel influenza A (H1N1) neuraminidase inhibitors from
Glycyrrhiza inflata. Bioorg. Med. Chem. Lett. 21:294–298. http://dx.doi
27. Avila HP, Smania EDF, Monache FD, Smania A, Jr. 2008. Structure-
activity relationship of antibacterial chalcones. Bioorg. Med. Chem. 16:
3. Brown DM, Upcroft JA, Upcroft P. 1996. A H2O-producing NADH
oxidase from the protozoan parasite Giardia duodenalis. Eur. J. Biochem.
4. Di Matteo A, Scandurra FM, Testa F, Forte E, Sarti P, Brunori M,
Giuffrè A. 2008. The O2-scavenging flavodiiron protein in the human
parasite Giardia intestinalis. J. Biol. Chem. 283:4061–4068. http://dx.doi
5. Mastronicola D, Testa F, Forte E, Bordi E, Pucillo LP, Sarti P, Giuffrè
A. 2010. Flavohemoglobin and nitric oxide detoxification in the human
protozoan parasite Giardia intestinalis. Biochem. Biophys. Res. Commun.
6. Mastronicola D, Giuffrè A, Testa F, Mura A, Forte E, Bordi E, Pucillo
LP, Fiori PL, Sarti P. 2011. Giardia intestinalis escapes oxidative stress by
colonizing the small intestine: a molecular hypothesis. IUBMB Life 63:21–
7. Testa F, Mastronicola D, Cabelli DE, Bordi E, Pucillo LP, Sarti P,
Saraiva LM, Giuffrè A, Teixeira M. 2011. The superoxide reductase from
the early diverging eukaryote Giardia intestinalis. Free Radic. Biol. Med.
8. Berkman DS, Lescano AG, Gilman RH, Lopez SL, Black MM. 2002.
Effects of stunting, diarrhoeal disease, and parasitic infection during in-
fancy on cognition in late childhood: a follow-up study. Lancet 359:564–
28. Chiaradia LD, Martins PG, Cordeiro MN, Guido RV, Ecco G, Andri-
copulo AD, Yunes RA, Vernal J, Nunes RJ, Terenzi H. 2012. Synthesis,
biological evaluation, and molecular modeling of chalcone derivatives as
potent inhibitors of Mycobacterium tuberculosis protein tyrosine phospha-
9. Hanevik K, Hausken T, Morken MH, Strand EA, Morch K, Coll P,
Helgeland L, Langeland N. 2007. Persisting symptoms and duodenal
inflammation related to Giardia duodenalis infection. J. Infect. 55:524–
29. Sivakumar PM, Muthu Kumar T, Doble M. 2009. Antifungal activity,
mechanism and QSAR studies on chalcones. Chem. Biol. Drug Des. 74:
30. Zuo Y, Yu Y, Wang S, Shao W, Zhou B, Lin L, Luo Z, Huang R, Du J,
Bu X. 2012. Synthesis and cytotoxicity evaluation of biaryl-based chal-
cones and their potential in TNFalpha-induced nuclear factor-kappaB
31. Quintin J, Desrivot J, Thoret S, Le Menez P, Cresteil T, Lewin G. 2009.
Synthesis and biological evaluation of a series of tangeretin-derived chal-
32. Won SJ, Liu CT, Tsao LT, Weng JR, Ko HH, Wang JP, Lin CN. 2005.
Synthetic chalcones as potential anti-inflammatory and cancer chemopre-
33. Montes-Avila J, Diaz-Camacho SP, Sicairos-Felix J, Delgado-Vargas
F, Rivero IA. 2009. Solution-phase parallel synthesis of substituted
chalcones and their antiparasitary activity against Giardia lamblia.
10. Ali V, Nozaki T. 2007. Current therapeutics, their problems, and sulfur-
containing-amino-acid metabolism as a novel target against infections by
“amitochondriate” protozoan parasites. Clin. Microbiol. Rev. 20:164–
11. Tejman-Yarden N, Eckmann L. 2011. New approaches to the treatment
12. Edwards DI. 1993. Nitroimidazole drugs—action and resistance mecha-
nisms. I. Mechanisms of action. J. Antimicrob. Chemother. 31:9–20. http:
13. Upcroft P, Upcroft JA. 2001. Drug targets and mechanisms of resistance
in the anaerobic protozoa. Clin. Microbiol. Rev. 14:150–164. http://dx
14. Espey MG. 2013. Role of oxygen gradients in shaping redox relationships
between the human intestine and its microbiota. Free Radic. Biol. Med.
15. Gillin FD, Reiner DS. 1982. Effects of oxygen tension and reducing agents
on sensitivity of Giardia lamblia to metronidazole in vitro. Biochem. Phar-
16. Paget T, Maroulis S, Mitchell A, Edwards MR, Jarroll EL, Lloyd D.
2004. Menadione kills trophozoites and cysts of Giardia intestinalis. Mi-
17. Müller J, Ruhle G, Müller N, Rossignol JF, Hemphill A. 2006. In vitro
effects of thiazolides on Giardia lamblia WB clone C6 cultured axenically
and in coculture with Caco2 cells. Antimicrob. Agents Chemother. 50:
34. Khatib S, Nerya O, Musa R, Shmuel M, Tamir S, Vaya J. 2005.
Chalcones as potent tyrosinase inhibitors: the importance of a 2,4-
substituted resorcinol moiety. Bioorg. Med. Chem. 13:433–441. http://dx
35. Sriwilaijaroen N, Liu M, Go ML, Wilairat P. 2006. Plasmepsin II inhib-
Antimicrobial Agents and Chemotherapy