20. McNamara CW, Lee MC et al (2013) Targeting Plasmodium PI(4)K to eliminate malaria.
Nature 504:248–253
21. Achieng AO, Rawat M et al (2017) Antimalarials: molecular drug targets and mechanism of
action. Curr Top Med Chem 17:2114–2128
22. Melo AM, Bandeiras TM, Teixeira M (2004) New insights into type II NAD (P) H: quinone
oxidoreductases. Microbiol Mol Biol Rev 68:603–616
23. Biagini GA, Viriyavejakul P et al (2006) Functional characterization and target validation of
alternative complex I of Plasmodium falciparum mitochondria. Antimicrob Agents
Chemother 50:1841–1851
24. Pidathala C, Amewu R et al (2012) Identification, design and biological evaluation of bisaryl
quinolones targeting Plasmodium falciparum type II NADH: quinone oxidoreductase
(PfNDH2). J Med Chem 55:1831–1843
25. Yang Y, Yu Y et al (2017) Target elucidation by cocrystal structures of NADH-ubiquinone
oxidoreductase of Plasmodium falciparum (PfNDH2) with small molecule to eliminate
drug-resistant malaria. J Med Chem 60:1994–2005
26. Rodrigues T, Lopes F, Moreira R (2010) Inhibitors of the mitochondrial electron transport
chain and de novo pyrimidine biosynthesis as antimalarials: the present status. Curr Med
Chem 17:929–956
27. Alnabulsi S, Santina E et al (2016) Non-symmetrical furan-amidines as novel leads for the
treatment of cancer and malaria. Eur J Med Chem 111:33–45
28. Banerjee AK, Arora N, Murty USN (2012) Aspartate carbamoyltransferase of Plasmodium
falciparum as a potential drug target for designing anti-malarial chemotherapeutic agents.
Med Chem Res 21:2480–2493
29. [a] Lunev S, Bosch SS et al. (2016) Crystal structure of truncated aspartate transcarbamoylase
from Plasmodium falciparum. Acta Crystallogr F 72:523–533; [b] Lunev S, Bosch SS et al.
(2018) Identification of a non-competitive Inhibitor of Plasmodium falciparum aspartate
transcarbamoylase. Biochem Biophys Res Commun 497:835–842
30. Fritz-Wolf K, Jortzik E et al (2013) Crystal structure of the Plasmodium falciparum
thioredoxin reductase-thioredoxin complex. J Mol Biol 425:3446–3460
31. McMillan PJ, Arscott LD et al (2006) Identification of acid-base catalytic residues of high-M r
thioredoxin reductase from Plasmodium falciparum. J Biol Chem 281:32967–32977
32. Boumis G, Giardina G et al (2012) Crystal structure of Plasmodium falciparum thioredoxin
reductase, a validated drug target. Biochem Biophys Res Commun 425:806–811
33. McCarty SE, Schellenberger A et al (2015) Plasmodium falciparum thioredoxin reductase
(PfTrxR) and its role as a target for new antimalarial discovery. Molecules 20:11459–11473
34. Munigunti R, Gathiaka S et al (2013) Characterization of PfTrxR inhibitors using antimalarial
assays and in silico techniques. Chem Cent J 7:175
35. Munigunti R, Gathiaka S et al (2014) Determination of antiplasmodial activity and binding
affinity of curcumin and demethoxycurcumin towards PfTrxR. Nat Prod Res 28:359–364
36. Winkler M, Maynadier M et al (2015) Uncovering new structural insights for antimalarial
activity from cost-effective aculeatin-like derivatives. Org Biomol Chem 13:2064–2077
37. Chaal BK, Gupta AP et al (2010) Histone deacetylases play a major role in the transcriptional
regulation of the Plasmodium falciparum life cycle. PLoS Path 6:e1000737
38. [a] Gupta AP, Bozdech Z (2017) Epigenetic landscapes underlining global patterns of gene
expression in the human malaria parasite, Plasmodium falciparum. Int J Parasitol 47:399–
407; [b] Sumanadasa SDM, Goodman CD et al. (2012) Antimalarial activity of the anticancer
histone deacetylase inhibitor SB939. Antimicrob Agents Chemother 56:3849–3856
39. Mukherjee P, Pradhan A et al (2008) Structural insights into the Plasmodium falciparum
histone deacetylase 1 (PfHDAC-1): a novel target for the development of antimalarial therapy.
Bioorg Med Chem 16:5254–5265
40. Hansen FK, Sumanadasa SDM et al. Discovery of HDAC inhibitors with potent activity
against multiple malaria parasite life cycle stages. Eur J Med Chem 82:204–213
41. Darkin-Rattray SJ, Gurnett AM et al (1996) Apicidin: a novel antiprotozoal agent that inhibits
parasite histone deacetylase. Proc Natl Acad Sci USA 93:13143–13147
Structure-Based Design of PfDHODH Inhibitors …
217
Nature 504:248–253
21. Achieng AO, Rawat M et al (2017) Antimalarials: molecular drug targets and mechanism of
action. Curr Top Med Chem 17:2114–2128
22. Melo AM, Bandeiras TM, Teixeira M (2004) New insights into type II NAD (P) H: quinone
oxidoreductases. Microbiol Mol Biol Rev 68:603–616
23. Biagini GA, Viriyavejakul P et al (2006) Functional characterization and target validation of
alternative complex I of Plasmodium falciparum mitochondria. Antimicrob Agents
Chemother 50:1841–1851
24. Pidathala C, Amewu R et al (2012) Identification, design and biological evaluation of bisaryl
quinolones targeting Plasmodium falciparum type II NADH: quinone oxidoreductase
(PfNDH2). J Med Chem 55:1831–1843
25. Yang Y, Yu Y et al (2017) Target elucidation by cocrystal structures of NADH-ubiquinone
oxidoreductase of Plasmodium falciparum (PfNDH2) with small molecule to eliminate
drug-resistant malaria. J Med Chem 60:1994–2005
26. Rodrigues T, Lopes F, Moreira R (2010) Inhibitors of the mitochondrial electron transport
chain and de novo pyrimidine biosynthesis as antimalarials: the present status. Curr Med
Chem 17:929–956
27. Alnabulsi S, Santina E et al (2016) Non-symmetrical furan-amidines as novel leads for the
treatment of cancer and malaria. Eur J Med Chem 111:33–45
28. Banerjee AK, Arora N, Murty USN (2012) Aspartate carbamoyltransferase of Plasmodium
falciparum as a potential drug target for designing anti-malarial chemotherapeutic agents.
Med Chem Res 21:2480–2493
29. [a] Lunev S, Bosch SS et al. (2016) Crystal structure of truncated aspartate transcarbamoylase
from Plasmodium falciparum. Acta Crystallogr F 72:523–533; [b] Lunev S, Bosch SS et al.
(2018) Identification of a non-competitive Inhibitor of Plasmodium falciparum aspartate
transcarbamoylase. Biochem Biophys Res Commun 497:835–842
30. Fritz-Wolf K, Jortzik E et al (2013) Crystal structure of the Plasmodium falciparum
thioredoxin reductase-thioredoxin complex. J Mol Biol 425:3446–3460
31. McMillan PJ, Arscott LD et al (2006) Identification of acid-base catalytic residues of high-M r
thioredoxin reductase from Plasmodium falciparum. J Biol Chem 281:32967–32977
32. Boumis G, Giardina G et al (2012) Crystal structure of Plasmodium falciparum thioredoxin
reductase, a validated drug target. Biochem Biophys Res Commun 425:806–811
33. McCarty SE, Schellenberger A et al (2015) Plasmodium falciparum thioredoxin reductase
(PfTrxR) and its role as a target for new antimalarial discovery. Molecules 20:11459–11473
34. Munigunti R, Gathiaka S et al (2013) Characterization of PfTrxR inhibitors using antimalarial
assays and in silico techniques. Chem Cent J 7:175
35. Munigunti R, Gathiaka S et al (2014) Determination of antiplasmodial activity and binding
affinity of curcumin and demethoxycurcumin towards PfTrxR. Nat Prod Res 28:359–364
36. Winkler M, Maynadier M et al (2015) Uncovering new structural insights for antimalarial
activity from cost-effective aculeatin-like derivatives. Org Biomol Chem 13:2064–2077
37. Chaal BK, Gupta AP et al (2010) Histone deacetylases play a major role in the transcriptional
regulation of the Plasmodium falciparum life cycle. PLoS Path 6:e1000737
38. [a] Gupta AP, Bozdech Z (2017) Epigenetic landscapes underlining global patterns of gene
expression in the human malaria parasite, Plasmodium falciparum. Int J Parasitol 47:399–
407; [b] Sumanadasa SDM, Goodman CD et al. (2012) Antimalarial activity of the anticancer
histone deacetylase inhibitor SB939. Antimicrob Agents Chemother 56:3849–3856
39. Mukherjee P, Pradhan A et al (2008) Structural insights into the Plasmodium falciparum
histone deacetylase 1 (PfHDAC-1): a novel target for the development of antimalarial therapy.
Bioorg Med Chem 16:5254–5265
40. Hansen FK, Sumanadasa SDM et al. Discovery of HDAC inhibitors with potent activity
against multiple malaria parasite life cycle stages. Eur J Med Chem 82:204–213
41. Darkin-Rattray SJ, Gurnett AM et al (1996) Apicidin: a novel antiprotozoal agent that inhibits
parasite histone deacetylase. Proc Natl Acad Sci USA 93:13143–13147
Structure-Based Design of PfDHODH Inhibitors …
217