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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

New Molecular Targets and Strategies for Antimalarial Discovery

Author(s): Anna Caroline Aguiar, Lorena R.F. de Sousa, Celia R.S. Garcia, Glaucius Oliva and Rafael V.C. Guido*

Volume 26 , Issue 23 , 2019

Page: [4380 - 4402] Pages: 23

DOI: 10.2174/0929867324666170830103003

Price: $65


Malaria remains a major health problem, especially because of the emergence of resistant P. falciparum strains to artemisinin derivatives. In this context, safe and affordable antimalarial drugs are desperately needed. New proteins have been investigated as molecular targets for research and development of innovative compounds with welldefined mechanism of action. In this review, we highlight genetically and clinically validated plasmodial proteins as drug targets for the next generation of therapeutics. The enzymes described herein are involved in hemoglobin hydrolysis, the invasion process, elongation factors for protein synthesis, pyrimidine biosynthesis, post-translational modifications such as prenylation, phosphorylation and histone acetylation, generation of ATP in mitochondrial metabolism and aminoacylation of RNAs. Significant advances on proteomics, genetics, structural biology, computational and biophysical methods provided invaluable molecular and structural information about these drug targets. Based on this, several strategies and models have been applied to identify and improve lead compounds. This review presents the recent progresses in the discovery of antimalarial drug candidates, highlighting the approaches, challenges, and perspectives to deliver affordable, safe and low single-dose medicines to treat malaria.

Keywords: Plasmodium spp, malaria, enzymes, molecular target, antimalarial, inhibitor.

WHO, 2016.. accessed in September 2016.
Sturm, A.; Amino, R.; van de Sand, C.; Regen, T.; Retzlaff, S.; Rennenberg, A.; Krueger, A.; Pollok, J.M.; Menard, R.; Heussler, V.T. Manipulation of host hepatocytes by the malaria parasite for delivery into liver sinusoids. Science, 2006, 313(5791), 1287-1290.
[] [PMID: 16888102]
Cowman, A.F.; Berry, D.; Baum, J. The cellular and molecular basis for malaria parasite invasion of the human red blood cell. J. Cell Biol., 2012, 198(6), 961-971.
[] [PMID: 22986493]
Michon, P1.; Fraser, T.; Adams, J.H. Naturally acquired and vaccine-elicited antibodies block erythrocyte cytoadherence of the Plasmodium vivax Duffy binding protein. Infect. Immun., 2000, 68(6), 3164-3171.
Idro, R.; Marsh, K.; John, C.C.; Newton, C.R.J. Cerebral malaria: mechanisms of brain injury and strategies for improved neurocognitive outcome. Pediatr. Res., 2010, 68(4), 267-274.
[] [PMID: 20606600]
Dondorp, A.M.; Nosten, F.; Yi, P.; Das, D.; Phyo, A.P.; Tarning, J.; Lwin, K.M.; Ariey, F.; Hanpithakpong, W.; Lee, S.J.; Ringwald, P.; Silamut, K.; Imwong, M.; Chotivanich, K.; Lim, P.; Herdman, T.; An, S.S.; Yeung, S.; Singhasivanon, P.; Day, N.P.; Lindegardh, N.; Socheat, D.; White, N.J. Artemisinin resistance in Plasmodium falciparum malaria. N. Engl. J. Med., 2009, 361(5), 455-467.
[] [PMID: 19641202]
Lin, J.T.; Juliano, J.J.; Wongsrichanalai, C. Drug-Resistant Malaria: The Era of ACT. Curr. Infect. Dis. Rep., 2010, 12(3), 165-173.
[] [PMID: 21308525]
Miotto, O.; Almagro-Garcia, J.; Manske, M.; Macinnis, B.; Campino, S.; Rockett, K.A.; Amaratunga, C.; Lim, P.; Suon, S.; Sreng, S.; Anderson, J.M.; Duong, S.; Nguon, C.; Chuor, C.M.; Saunders, D.; Se, Y.; Lon, C.; Fukuda, M.M.; Amenga-Etego, L.; Hodgson, A.V.; Asoala, V.; Imwong, M.; Takala-Harrison, S.; Nosten, F.; Su, X.Z.; Ringwald, P.; Ariey, F.; Dolecek, C.; Hien, T.T.; Boni, M.F.; Thai, C.Q.; Amambua-Ngwa, A.; Conway, D.J.; Djimdé, A.A.; Doumbo, O.K.; Zongo, I.; Ouedraogo, J.B.; Alcock, D.; Drury, E.; Auburn, S.; Koch, O.; Sanders, M.; Hubbart, C.; Maslen, G.; Ruano-Rubio, V.; Jyothi, D.; Miles, A.; O’Brien, J.; Gamble, C.; Oyola, S.O.; Rayner, J.C.; Newbold, C.I.; Berriman, M.; Spencer, C.C.; McVean, G.; Day, N.P.; White, N.J.; Bethell, D.; Dondorp, A.M.; Plowe, C.V.; Fairhurst, R.M.; Kwiatkowski, D.P. Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia. Nat. Genet., 2013, 45(6), 648-655.
[] [PMID: 23624527]
Ashley, E.A.; Dhorda, M.; Fairhurst, R.M.; Amaratunga, C.; Lim, P.; Suon, S.; Sreng, S.; Anderson, J.M.; Mao, S.; Sam, B.; Sopha, C.; Chuor, C.M.; Nguon, C.; Sovannaroth, S.; Pukrittayakamee, S.; Jittamala, P.; Chotivanich, K.; Chutasmit, K.; Suchatsoonthorn, C.; Runcharoen, R.; Hien, T.T.; Thuy-Nhien, N.T.; Thanh, N.V.; Phu, N.H.; Htut, Y.; Han, K.T.; Aye, K.H.; Mokuolu, O.A.; Olaosebikan, R.R.; Folaranmi, O.O.; Mayxay, M.; Khanthavong, M.; Hongvanthong, B.; Newton, P.N.; Onyamboko, M.A.; Fanello, C.I.; Tshefu, A.K.; Mishra, N.; Valecha, N.; Phyo, A.P.; Nosten, F.; Yi, P.; Tripura, R.; Borrmann, S.; Bashraheil, M.; Peshu, J.; Faiz, M.A.; Ghose, A.; Hossain, M.A.; Samad, R.; Rahman, M.R.; Hasan, M.M.; Islam, A.; Miotto, O.; Amato, R.; MacInnis, B.; Stalker, J.; Kwiatkowski, D.P.; Bozdech, Z.; Jeeyapant, A.; Cheah, P.Y.; Sakulthaew, T.; Chalk, J.; Intharabut, B.; Silamut, K.; Lee, S.J.; Vihokhern, B.; Kunasol, C.; Imwong, M.; Tarning, J.; Taylor, W.J.; Yeung, S.; Woodrow, C.J.; Flegg, J.A.; Das, D.; Smith, J.; Venkatesan, M.; Plowe, C.V.; Stepniewska, K.; Guerin, P.J.; Dondorp, A.M.; Day, N.P.; White, N.J. Tracking Resistance to Artemisinin Collaboration (TRAC). Spread of artemisinin resistance in Plasmodium falciparum malaria. N. Engl. J. Med., 2014, 371(5), 411-423.
[] [PMID: 25075834]
Ariey, F.; Witkowski, B.; Amaratunga, C.; Beghain, J.; Langlois, A.C.; Khim, N.; Kim, S.; Duru, V.; Bouchier, C.; Ma, L.; Lim, P.; Leang, R.; Duong, S.; Sreng, S.; Suon, S.; Chuor, C.M.; Bout, D.M.; Ménard, S.; Rogers, W.O.; Genton, B.; Fandeur, T.; Miotto, O.; Ringwald, P.; Le Bras, J.; Berry, A.; Barale, J.C.; Fairhurst, R.M.; Benoit-Vical, F.; Mercereau-Puijalon, O.; Ménard, D. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature, 2014, 505(7481), 50-55.
[] [PMID: 24352242]
Flannery, E.L.; Chatterjee, A.K.; Winzeler, E.A. Antimalarial drug discovery - approaches and progress towards new medicines. Nat. Rev. Microbiol., 2013, 11(12), 849-862.
[] [PMID: 24217412]
Winzeler, E.A.; Manary, M.J. Drug resistance genomics of the antimalarial drug artemisinin. Genome Biol., 2014, 15(11), 544-556.
[] [PMID: 25470531]
Young, J.A.; Winzeler, E.A. Using expression information to discover new drug and vaccine targets in the malaria parasite Plasmodium falciparum. Pharmacogenomics, 2005, 6(1), 17-26.
[] [PMID: 15723602]
Liñares, G.E.; Rodriguez, J.B. Current status and progresses made in malaria chemotherapy. Curr. Med. Chem., 2007, 14(3), 289-314.
[] [PMID: 17305534]
Birkholtz, L.; van Brummelen, A.C.; Clark, K.; Niemand, J.; Maréchal, E.; Llinás, M.; Louw, A.I. Exploring functional genomics for drug target and therapeutics discovery in Plasmodia. Acta Trop., 2008, 105(2), 113-123.
[] [PMID: 18083131]
Hopkins, A.L.; Groom, C.R. The druggable genome. Nature Rev. Drug Discov.1, 2002, (9), 727-730.
Robertson, J.G. Mechanistic basis of enzyme-targeted drugs. Biochemistry, 2005, 44(15), 5561-5571.
[] [PMID: 15823014]
Terstappen, G.C.; Schlüpen, C.; Raggiaschi, R.; Gaviraghi, G. Target deconvolution strategies in drug discovery. Nat. Rev. Drug Discov., 2007, 6(11), 891-903.
[] [PMID: 17917669]
Sleno, L.; Emili, A. Proteomic methods for drug target discovery. Curr. Opin. Chem. Biol., 2008, 12(1), 46-54.
[] [PMID: 18282485]
Wells, T.N.; Hooft van Huijsduijnen, R.; Van Voorhis, W.C. Malaria medicines: A glass half full? Nat. Rev. Drug Discov., 2015, 14(6), 424-442.
[] [PMID: 26000721]
Wang, J.; Hou, T. Advances in computationally modeling human oral bioavailability. Adv. Drug Deliv. Rev., 2015, 86, 11-16.
[] [PMID: 25582307]
Younis, Y.; Street, L.J.; Waterson, D.; Witty, M.J.; Chibale, K. Cell-based medicinal chemistry optimization of high throughput screening hits for orally active antimalarials. Part 2: Hits fromSoftFocus Kinase and other Libraries. Miniperspectives series on phenotypic screening for antiinfective targets. J. Med. Chem., 2013, 56, 7750-7754.
[] [PMID: 23927599]
Honarparvar, B.; Govender, T.; Maguire, G.E.M.; Soliman, M.E.S.; Kruger, H.G. Integrated approach to structure-based enzymatic drug design: molecular modeling, spectroscopy, and experimental bioactivity. Chem. Rev., 2014, 114(1), 493-537.
[] [PMID: 24024775]
Zheng, H.; Hou, J.; Zimmerman, M.D.; Wlodawer, A.; Minor, W. The future of crystallography in drug discovery. Expert Opin. Drug Discov., 2014, 9(2), 125-137.
[] [PMID: 24372145]
Wienken, C.J.; Baaske, P.; Rothbauer, U.; Braun, D.; Duhr, S. Protein-binding assays in biological liquids using microscale thermophoresis. Nat. Commun., 2010, 1(100), 100.
[] [PMID: 20981028]
Shanmuganathan, M.; Britz-McKibbin, P. High quality drug screening by capillary electrophoresis: a review. Anal. Chim. Acta, 2013, 773, 24-36.
[] [PMID: 23561903]
ShuJi. Y.; Yi, L. Advanced experimental methods toward understanding biophysicochemical interactions of interfacial biomolecules by using sum frequency generation vibrational spectroscopy. Sci. China Chem., 2014, 57(12), 1646-1661.
Huang, Y.; Zhang, Q.; Liu, G.; Zhao, R. A continuous-flow mass biosensor for the real-time dynamic analysis of protease inhibition. Chem. Commun. (Camb.), 2015, 51(30), 6601-6604.
[] [PMID: 25776796]
Garcia, C.R.; de Azevedo, M.F.; Wunderlich, G.; Budu, A.; Young, J.A.; Bannister, L. Plasmodium in the postgenomic era: New insights into the molecular cell biology of malaria parasites. Int. Rev. Cell Mol. Biol., 2008, 266, 85-156.
[] [PMID: 18544493]
Avitia-Domínguez, C.; Sierra-Campos, E.; Betancourt-Conde, I.; Aguirre-Raudry, M.; Vázquez-Raygoza, A.; Luevano-De la Cruz, A.; Favela-Candia, A.; Sarabia-Sanchez, M.; Ríos-Soto, L.; Méndez-Hernández, E.; Cisneros-Martínez, J.; Palacio-Gastélum, M.G.; Valdez-Solana, M.; Hernández-Rivera, J.; De Lira-Sánchez, J.; Campos-Almazán, M.; Téllez-Valencia, A. Targeting plasmodium metabolism to improve antimalarial drug design. Curr. Protein Pept. Sci., 2016, 17(3), 260-274.
[] [PMID: 26983887]
Otto, H.H.; Schirmeister, T. Cysteine proteases and their inhibitors. Chem. Rev., 1997, 97(1), 133-172.
[] [PMID: 11848867]
Kominami, E.; Kunio, I.; Katunuma, N. Activation of the intramyofibral autophagic-lysosomal system in muscular dystrophy. Am. J. Pathol., 1987, 127(3), 461-466.
[PMID: 3296770]
Fusetani, N.; Fujita, M.; Nakao, Y.; Matsunaga, S.; Van Soest, R.W. Tokaramide A, a new cathepsin B inhibitor from the marine sponge Theonella aff. mirabilis. Bioorg. Med. Chem. Lett., 1999, 9(24), 3397-3402.
[] [PMID: 10617079]
Yasuda, Y.; Kaleta, J.; Brömme, D. The role of cathepsins in osteoporosis and arthritis: rationale for the design of new therapeutics. Adv. Drug Deliv. Rev., 2005, 57(7), 973-993.
[] [PMID: 15876399]
Turk, B. Targeting proteases: successes, failures and future prospects. Nat. Rev. Drug Discov., 2006, 5(9), 785-799.
[] [PMID: 16955069]
Zhao, Q.; Jia, Y.; Xiao, Y. Cathepsin K: a therapeutic target for bone diseases. Biochem. Biophys. Res. Commun., 2009, 380(4), 721-723.
[] [PMID: 19338743]
De Clercq, E.; Li, G. Approved antiviral drugs over the past 50 years. Clin. Microbiol. Rev., 2016, 29(3), 695-747.
[] [PMID: 27281742]
Drag, M.; Salvesen, G.S. Emerging principles in protease-based drug discovery. Nat. Rev. Drug Discov., 2010, 9(9), 690-701.
[] [PMID: 20811381]
Francis, S.E.; Sullivan, D.J., Jr; Goldberg, D.E. Hemoglobin metabolism in the malaria parasite Plasmodium falciparum. Annu. Rev. Microbiol., 1997, 51, 97-123.
[] [PMID: 9343345]
Eggleson, K.K.; Duffin, K.L.; Goldberg, D.E.J. Identification and characterization of falcilysin, a metallopeptidase involved in hemoglobin catabolism within the malaria parasite Plasmodium falciparum. J. Biol. Chem., 1999, 274(45), 32411-32417.
[] [PMID: 10542284]
Rosenthal, P.J.; Sijwali, P.S.; Singh, A.; Shenai, B.R. Cysteine proteases of malaria parasites: Targets for chemotherapy. Curr. Pharm. Des., 2002, 8(18), 1659-1672.
[] [PMID: 12132997]
Banerjee, R.; Liu, J.; Beatty, W.; Pelosof, L.; Klemba, M.; Goldberg, D.E. Four plasmepsins are active in the Plasmodium falciparum food vacuole, including a protease with an active-site histidine. Proc. Natl. Acad. Sci., 2002, 99, 990-995.
Shenai, B.R.; Sijwali, P.S.; Singh, A.; Rosenthal, P.J. Characterization of native and recombinant falcipain-2, a principal trophozoite cysteine protease and essential hemoglobinase of Plasmodium falciparum. J. Biol. Chem., 2000, 275(37), 29000-29010.
[] [PMID: 10887194]
Sijwali, P.S.; Brinen, L.S.; Rosenthal, P.J. Systematic optimization of expression and refolding of the Plasmodium falciparum cysteine protease falcipain-2. Protein Expr. Purif., 2001, 22(1), 128-134.
[] [PMID: 11388810]
Sijwali, P.S.; Rosenthal, P.J. Gene disruption confirms a critical role for the cysteine protease falcipain-2 in hemoglobin hydrolysis by Plasmodium falciparum. Proc. Natl. Acad. Sci. USA, 2004, 101(13), 4384-4389.
[] [PMID: 15070727]
Ettari, R.; Zappalà, M.; Micale, N.; Schirmeister, T.; Gelhaus, C.; Leippe, M.; Evers, A.; Grasso, S. Synthesis of novel peptidomimetics as inhibitors of protozoan cysteine proteases falcipain-2 and rhodesain. Eur. J. Med. Chem., 2010, 45(7), 3228-3233.
[] [PMID: 20434817]
Machon, U.; Büchold, C.; Stempka, M.; Schirmeister, T.; Gelhaus, C.; Leippe, M.; Gut, J.; Rosenthal, P.J.; Kisker, C.; Leyh, M.; Schmuck, C. On-bead screening of a combinatorial fumaric acid derived peptide library yields antiplasmodial cysteine protease inhibitors with unusual peptide sequences. J. Med. Chem., 2009, 52(18), 5662-5672.
[] [PMID: 19715342]
Hanspal, M.; Dua, M.; Takakuwa, Y.; Chishti, A.H.; Mizuno, A. Plasmodium falciparum cysteine protease falcipain-2 cleaves erythrocyte membrane skeletal proteins at late stages of parasite development. Blood, 2002, 100(3), 1048-1054.
[] [PMID: 12130521]
Krungkrai, J.; Prapunwattana, P.; Krungkrai, S.R. Ultrastructure and function of mitochondria in gametocytic stage of Plasmodium falciparum. Parasite, 2000, 7(1), 19-26.
[] [PMID: 10743643]
Wang, S.X.; Pandey, K.C.; Somoza, J.R.; Sijwali, P.S.; Kortemme, T.; Brinen, L.S.; Fletterick, R.J.; Rosenthal, P.J.; McKerrow, J.H. Structural basis for unique mechanisms of folding and hemoglobin binding by a malarial protease. Proc. Natl. Acad. Sci. USA, 2006, 103(31), 11503-11508.
[] [PMID: 16864794]
Guido, R.V.; Oliva, G.; Andricopulo, A.D. Virtual screening and its integration with modern drug design technologies. Curr. Med. Chem., 2008, 15(1), 37-46.
[] [PMID: 18220761]
Li, H.; Huang, J.; Chen, L.; Liu, X.; Chen, T.; Zhu, J.; Lu, W.; Shen, X.; Li, J.; Hilgenfeld, R.; Jiang, H. Identification of novel falcipain-2 inhibitors as potential antimalarial agents through structure-based virtual screening. J. Med. Chem., 2009, 52(15), 4936-4940.
[] [PMID: 19586036]
Wang, L.; Zhang, S.; Zhu, J.; Zhu, L.; Liu, X.; Shan, L.; Huang, J.; Zhang, W.; Li, H. Identification of diverse natural products as falcipain-2 inhibitors through structure-based virtual screening. Bioorg. Med. Chem. Lett., 2014, 24(5), 1261-1264.
[] [PMID: 24530004]
Danishuddin, M.; Khan, A.U. Structure based virtual screening to discover putative drug candidates: necessary considerations and successful case studies. Methods, 2015, 71, 135-145.
[] [PMID: 25448480]
Reiss, Y.; Goldstein, J.L.; Seabra, M.C.; Casey, P.J.; Brown, M.S. Inhibition of purified p21ras farnesyl: protein transferase by Cys-AAX tetrapeptides Cell, 1990, 62, 81e88.
Clarke, S. Protein isoprenylation and methylation at carboxyl-terminal cysteine residues. Annu. Rev. Biochem., 1992, 61, 355-386.
[] [PMID: 1497315]
Zhang, F.L.; Casey, P.J. Protein prenylation: molecular mechanisms and functional consequences. Annu. Rev. Biochem., 1996, 65, 241-269.
[] [PMID: 8811180]
Eastman, R.T.; Buckner, F.S.; Yokoyama, K.; Gelb, M.H.; Van Voorhis, W.C. Fighting parasitic disease by blocking protein farnesylation J. Lipid Res., 2006, 47, 233e240.
Ochocki, J.D.; Distefano, M.D. Prenyltransferase inhibitors: treating human ailments from cancer to parasitic infections. MedChemComm, 2013, 4(3), 476-492.
[] [PMID: 25530833]
Chakrabarti, D.; Da Silva, T.; Barger, J.; Paquette, S.; Patel, H.; Patterson, S.; Allen, C.M. Protein farnesyltransferase and protein prenylation in Plasmodium falciparum. J. Biol. Chem., 2002, 277(44), 42066-42073.
[] [PMID: 12194969]
Qidwai, T.; Jamal, F.; Khan, M.Y.; Sharma, B. Exploring drug targets in isoprenoid biosynthetic pathway for plasmodium falciparum. Biochem. Res. Int., 2014.2014657189
[] [PMID: 24864210]
Leonard, D.M. Ras farnesyltransferase: a new therapeutic target. J. Med. Chem., 1997, 40(19), 2971-2990.
[] [PMID: 9301658]
Cox, A.D.; Der, C.J. Ras family signaling: therapeutic targeting. Cancer Biol. Ther., 2002, 1(6), 599-606.
[] [PMID: 12642680]
Bell, I.M. Inhibitors of farnesyltransferase: a rational approach to cancer chemotherapy? J. Med. Chem., 2004, 47(8), 1869-1878.
[] [PMID: 15055985]
Nallan, L.; Bauer, K.D.; Bendale, P.; Rivas, K.; Yokoyama, K.; Hornéy, C.P.; Pendyala, P.R.; Floyd, D.; Lombardo, L.J.; Williams, D.K.; Hamilton, A.; Sebti, S.; Windsor, W.T.; Weber, P.C.; Buckner, F.S.; Chakrabarti, D.; Gelb, M.H.; Van Voorhis, W.C. Protein farnesyltransferase inhibitors exhibit potent antimalarial activity. J. Med. Chem., 2005, 48(11), 3704-3713.
[] [PMID: 15916422]
Eastman, R.T.; White, J.; Hucke, O.; Yokoyama, K.; Verlinde, C.L.; Hast, M.A.; Beese, L.S.; Gelb, M.H.; Rathod, P.K.; Van Voorhis, W.C. Resistance mutations at the lipid substrate binding site of Plasmodium falciparum protein farnesyltransferase. Mol. Biochem. Parasitol., 2007, 152(1), 66-71.
[] [PMID: 17208314]
Glenn, M.P.; Chang, S.Y.; Hornéy, C.; Rivas, K.; Yokoyama, K.; Pusateri, E.E.; Fletcher, S.; Cummings, C.G.; Buckner, F.S.; Pendyala, P.R.; Chakrabarti, D.; Sebti, S.M.; Gelb, M.; Van Voorhis, W.C.; Hamilton, A.D. Structurally simple, potent, Plasmodium selective farnesyltransferase inhibitors that arrest the growth of malaria parasites. J. Med. Chem., 2006, 49(19), 5710-5727.
[] [PMID: 16970397]
Kumar, P.M.; Raj, K.K.; Ramachandran, D.; Kumar, P.M.N.S.; Vaddavalli, R. An insight into structural and functional characteristics of Plasmodium falciparum Farnesyltransferase (PfFT) 3d7: Comparative modeling and docking studies. J. Proteomics Bioinform., 2010, 3, 305-309.
Fletcher, S.; Cummings, C.G.; Rivas, K.; Katt, W.P.; Hornéy, C.; Buckner, F.S.; Chakrabarti, D.; Sebti, S.M.; Gelb, M.H.; Van Voorhis, W.C.; Hamilton, A.D. Potent, Plasmodium-selective farnesyltransferase inhibitors that arrest the growth of malaria parasites: structure-activity relationships of ethylenediamine-analogue scaffolds and homology model validation. J. Med. Chem., 2008, 51(17), 5176-5197.
[] [PMID: 18686940]
Pradeep, K.M.; Kranthi, R.K.; Vaddavalli, R.; Pavan, K.M.N.S.; Aravind, K. Discovery of novel and potent molecules against Plasmodium falciparum farnesyltransferase (PfFT) by improved virtual screening strategy. Int J Drug Des Discov, 2011, 2, 666-673.
Xie, A.; Sivaprakasam, P.; Doerksen, R.J. 3D-QSAR analysis of antimalarial farnesyltransferase inhibitors based on a 2,5-diaminobenzophenone scaffold. Bioorg. Med. Chem., 2006, 14(21), 7311-7323.
[] [PMID: 16837204]
Equbal, T.; Silakari, O.; Ravikumar, M. Exploring three-dimensional quantitative structural activity relationship (3D-QSAR) analysis of SCH 66336 (Sarasar) analogues of farnesyltransferase inhibitors. Eur. J. Med. Chem., 2008, 43(1), 204-209.
[] [PMID: 17442459]
Puntambekar, D.S.; Giridhar, R.; Yadav, M.R. Insights into the structural requirements of farnesyltransferase inhibitors as potential anti-tumor agents based on 3D-QSAR CoMFA and CoMSIA models. Eur. J. Med. Chem., 2008, 43(1), 142-154.
[] [PMID: 17448576]
Xie, A.; Odde, S.; Prasanna, S.; Doerksen, R.J. Imidazole-containing farnesyltransferase inhibitors: 3D quantitative structure-activity relationships and molecular docking. J. Comput. Aided Mol. Des., 2009, 23(7), 431-448.
[] [PMID: 19479325]
Deeb, O.; Alfalah, S.; Freitas, M.P.; da Cunha, E.F.F.; Ramalho, T.C. Exploring MIA-QSARs for farnesyltransferase inhibitory effect of antimalarial compounds refined by docking simulations. J. Biophys. Chem., 2012, 3, 58-71.
Divakar, S.; Hariharan, S. 3D-QSAR studies on Plasmodium falciparam proteins: A mini-review. Comb. Chem. High Throughput Screen., 2015, 18(2), 188-198.
[] [PMID: 25543683]
Xie, A.; Odde, S.; Prasanna, S.; Doerksen, R.J. Imidazole-containing farnesyltransferase inhibitors: 3D quantitative structure-activity relationships and molecular docking. J. Comput. Aided Mol. Des., 2009, 23(7), 431-448.
[] [PMID: 19479325]
Phillips, M.A.; Rathod, P.K. Plasmodium dihydroorotate dehydrogenase: A promising target for novel anti-malarial chemotherapy. Infect. Disord. Drug Targets, 2010, 10(3), 226-239.
[] [PMID: 20334617]
Stocks, P.A.; Barton, V.; Antoine, T.; Biagini, G.A.; Ward, S.A.; O’Neill, P.M. Novel inhibitors of the Plasmodium falciparum electron transport chain. Parasitology, 2014, 141(1), 50-65.
[] [PMID: 24401337]
Ekland, E.H.; Fidock, D.A. Advances in understanding the genetic basis of antimalarial drug resistance. Curr. Opin. Microbiol., 2007, 10(4), 363-370.
[] [PMID: 17709280]
Painter, H.J.; Morrisey, J.M.; Mather, M.W.; Vaidya, A.B. Specific role of mitochondrial electron transport in blood-stage Plasmodium falciparum. Nature, 2007, 446(7131), 88-91.
[] [PMID: 17330044]
Marcinkeviciene, J.; Rogers, M.J.; Kopcho, L.; Jiang, W.; Wang, K.; Murphy, D.J.; Lippy, J.; Link, S.; Chung, T.D.; Hobbs, F.; Haque, T.; Trainor, G.L.; Slee, A.; Stern, A.M.; Copeland, R.A. Selective inhibition of bacterial dihydroorotate dehydrogenases by thiadiazolidinediones. Biochem. Pharmacol., 2000, 60(3), 339-342.
[] [PMID: 10856428]
Baldwin, J.; Farajallah, A.M.; Malmquist, N.A.; Rathod, P.K.; Phillips, M.A. Malarial dihydroorotate dehydrogenase. Substrate and inhibitor specificity. J. Biol. Chem., 2002, 277(44), 41827-41834.
[] [PMID: 12189151]
Hurt, D.E.; Widom, J.; Clardy, J. Structure of Plasmodium falciparum dihydroorotate dehydrogenase with a bound inhibitor. Acta Crystallogr. D Biol. Crystallogr., 2006, 62(Pt 3), 312-323.
[] [PMID: 16510978]
Deng, X.; Gujjar, R.; El Mazouni, F.; Kaminsky, W.; Malmquist, N.A.; Goldsmith, E.J.; Rathod, P.K.; Phillips, M.A. Structural plasticity of malaria dihydroorotate dehydrogenase allows selective binding of diverse chemical scaffolds. J. Biol. Chem., 2009, 284(39), 26999-27009.
[] [PMID: 19640844]
Gujjar, R.; Marwaha, A.; El Mazouni, F.; White, J.; White, K.L.; Creason, S.; Shackleford, D.M.; Baldwin, J.; Charman, W.N.; Buckner, F.S.; Charman, S.; Rathod, P.K.; Phillips, M.A. Identification of a metabolically stable triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor with antimalarial activity in mice. J. Med. Chem., 2009, 52(7), 1864-1872.
[] [PMID: 19296651]
Coteron, J.M.; Marco, M.; Esquivias, J.; Deng, X.; White, K.L.; White, J.; Koltun, M.; El Mazouni, F.; Kokkonda, S.; Katneni, K.; Bhamidipati, R.; Shackleford, D.M.; Angulo-Barturen, I.; Ferrer, S.B.; Jiménez-Díaz, M.B.; Gamo, F.J.; Goldsmith, E.J.; Charman, W.N.; Bathurst, I.; Floyd, D.; Matthews, D.; Burrows, J.N.; Rathod, P.K.; Charman, S.A.; Phillips, M.A. Structure-guided lead optimization of triazolopyrimidine-ring substituents identifies potent Plasmodium falciparum dihydroorotate dehydrogenase inhibitors with clinical candidate potential. J. Med. Chem., 2011, 54(15), 5540-5561.
[] [PMID: 21696174]
Deng, X.; Matthews, D.; Rathod, P.K.; Phillips, M.A. The X-ray structure of Plasmodium falciparum dihydroorotate dehydrogenase bound to a potent and selective N-phenylbenzamide inhibitor reveals novel binding-site interactions. Acta Crystallogr. F Struct. Biol. Commun., 2015, 71(Pt 5), 553-559.
[] [PMID: 25945708]
[89] accessed in September 2016.
Ward, G.E.; Fujioka, H.; Aikawa, M.; Miller, L.H. Staurosporine inhibits invasion of erythrocytes by malarial merozoites. Exp. Parasitol., 1994, 79(3), 480-487.
[] [PMID: 7957765]
Elabbadi, N.; Ancelin, M.L.; Vial, H.J. Characterization of phosphatidylinositol synthase and evidence of a polyphosphoinositide cycle in Plasmodium-infected erythrocytes. Mol. Biochem. Parasitol., 1994, 63(2), 179-192.
[] [PMID: 8008017]
Fruman, D.A.; Meyers, R.E.; Cantley, L.C. Phosphoinositide kinases. Annu. Rev. Biochem., 1998, 67, 481-507.
[] [PMID: 9759495]
Kruger, M.C.; Coetzee, M.; Haag, M.; Weiler, H. Long-chain polyunsaturated fatty acids: selected mechanisms of action on bone. Prog. Lipid Res., 2010, 49(4), 438-449.
[] [PMID: 20600307]
Brown, J.R.; Auger, K.R. Phylogenomics of phosphoinositide lipid kinases: perspectives on the evolution of second messenger signaling and drug discovery. BMC Evol. Biol., 2011, 11, 4-14.
[] [PMID: 21208444]
McNamara, C.W.; Lee, M.C.S.; Lim, C.S.; Lim, S.H.; Roland, J.; Simon, O.; Yeung, B.K.; Chatterjee, A.K.; McCormack, S.L.; Manary, M.J.; Zeeman, A.M.; Dechering, K.J.; Kumar, T.S.; Henrich, P.P.; Gagaring, K.; Ibanez, M.; Kato, N.; Kuhen, K.L.; Fischli, C.; Nagle, A.; Rottmann, M.; Plouffe, D.M.; Bursulaya, B.; Meister, S.; Rameh, L.; Trappe, J.; Haasen, D.; Timmerman, M.; Sauerwein, R.W.; Suwanarusk, R.; Russell, B.; Renia, L.; Nosten, F.; Tully, D.C.; Kocken, C.H.M.; Glynne, R.J.; Bodenreider, C.; Fidock, D.A.; Diagana, T.T.; Winzeler, E.A. Targeting Plasmodium PI(4)K to eliminate malaria. Nature, 2013, 504(7479), 248-253.
[] [PMID: 24284631]
Burke, J.E.; Inglis, A.J.; Perisic, O.; Masson, G.R.; McLaughlin, S.H.; Rutaganira, F.; Shokat, K.M.; Williams, R.L. Structures of PI4KIIIβ complexes show simultaneous recruitment of Rab11 and its effectors. Science, 2014, 30;344(6187), 1035.
Choudhary, C.; Kumar, C.; Gnad, F.; Nielsen, M.L.; Rehman, M.; Walther, T.C.; Olsen, J.V.; Mann, M. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science, 2009, 325(5942), 834-840.
[] [PMID: 19608861]
Andrews, K.T.; Tran, T.N.; Lucke, A.J.; Kahnberg, P.; Le, G.T.; Boyle, G.M.; Gardiner, D.L.; Skinner-Adams, T.S.; Fairlie, D.P. Potent antimalarial activity of histone deacetylase inhibitor analogues. Antimicrob. Agents Chemother., 2008, 52(4), 1454-1461.
[] [PMID: 18212103]
Andrews, K.T.; Gupta, A.P.; Tran, T.N.; Fairlie, D.P.; Gobert, G.N.; Bozdech, Z. Comparative gene expression profiling of P. falciparum malaria parasites exposed to three different histone deacetylase inhibitors. PLoS One, 2012, 7(2)e31847
[] [PMID: 22384084]
Marek, M.; Kannan, S.; Hauser, A.T.; Moraes Mourão, M.; Caby, S.; Cura, V.; Stolfa, D.A.; Schmidtkunz, K.; Lancelot, J.; Andrade, L.; Renaud, J.P.; Oliveira, G.; Sippl, W.; Jung, M.; Cavarelli, J.; Pierce, R.J.; Romier, C. Structural basis for the inhibition of histone deacetylase 8 (HDAC8), a key epigenetic player in the blood fluke Schistosoma mansoni. PLoS Pathog., 2013, 9(9)e1003645
[] [PMID: 24086136]
Melesina, J.; Robaa, D.; Pierce, R.J.; Romier, C.; Sippl, W. Homology modeling of parasite histone deacetylases to guide the structure-based design of selective inhibitors. J. Mol. Graph. Model., 2015, 62, 342-361.
[] [PMID: 26595183]
Hino, A.; Hirai, M.; Tanaka, T.Q.; Watanabe, Y.; Matsuoka, H.; Kita, K. Critical roles of the mitochondrial complex II in oocyst formation of rodent malaria parasite Plasmodium berghei. J. Biochem., 2012, 152(3), 259-268.
[] [PMID: 22628552]
Fry, M.; Webb, E.; Pudney, M. Effect of mitochondrial inhibitors on adenosinetriphosphate levels in Plasmodium falciparum. Comp. Biochem. Physiol. B, 1990, 96(4), 775-782.
[] [PMID: 2171868]
Carrasco, M.P.; Gut, J.; Rodrigues, T.; Ribeiro, M.H.; Lopes, F.; Rosenthal, P.J.; Moreira, R.; Dos Santos, D.J. Exploring the molecular basis of Qo bc1 complex inhibitors activity to find novel antimalarials hits. Mol. Inform., 2013, 32(7), 659-670.
[] [PMID: 27481771]
Fisher, N.; Meunier, B. Molecular basis of resistance to cytochrome bc1 inhibitors. FEMS Yeast Res., 2008, 8(2), 183-192.
[] [PMID: 18093133]
Mather, M.W.; Morrisey, J.M.; Vaidya, A.B. Hemozoin-free Plasmodium falciparum mitochondria for physiological and drug susceptibility studies. Mol. Biochem. Parasitol., 2010, 174(2), 150-153.
[] [PMID: 20674615]
Capper, M.J.; O’Neill, P.M.; Fisher, N.; Strange, R.W.; Moss, D.; Ward, S.A.; Berry, N.G.; Lawrenson, A.S.; Hasnain, S.S.; Biagini, G.A.; Antonyuk, S.V. Antimalarial 4(1H)-pyridones bind to the Qi site of cytochrome bc1. Proc. Natl. Acad. Sci. USA, 2015, 112(3), 755-760.
[] [PMID: 25564664]
Biagini, G.A.; Fisher, N.; Berry, N.; Stocks, P.A.; Meunier, B.; Williams, D.P.; Bonar-Law, R.; Bray, P.G.; Owen, A.; O’Neill, P.M.; Ward, S.A. Acridinediones: selective and potent inhibitors of the malaria parasite mitochondrial bc1 complex. Mol. Pharmacol., 2008, 73(5), 1347-1355.
[] [PMID: 18319379]
McPhillie, M.; Zhou, Y.; El Bissati, K.; Dubey, J.; Lorenzi, H.; Capper, M.; Lukens, A.K.; Hickman, M.; Muench, S.; Verma, S.K.; Weber, C.R.; Wheeler, K.; Gordon, J.; Sanders, J.; Moulton, H.; Wang, K.; Kim, T.K.; He, Y.; Santos, T.; Woods, S.; Lee, P.; Donkin, D.; Kim, E.; Fraczek, L.; Lykins, J.; Esaa, F.; Alibana-Clouser, F.; Dovgin, S.; Weiss, L.; Brasseur, G.; Wirth, D.; Kent, M.; Hood, L.; Meunieur, B.; Roberts, C.W.; Hasnain, S.S.; Antonyuk, S.V.; Fishwick, C.; McLeod, R. New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections. Sci. Rep., 2016, 6, 29179.
[] [PMID: 27412848]
Baragaña, B.; Hallyburton, I.; Lee, M.C.; Norcross, N.R.; Grimaldi, R.; Otto, T.D.; Proto, W.R.; Blagborough, A.M.; Meister, S.; Wirjanata, G.; Ruecker, A.; Upton, L.M.; Abraham, T.S.; Almeida, M.J.; Pradhan, A.; Porzelle, A. Martínez. M.S.; Bolscher, J.M.; Woodland, A.; Norval, S.; Zuccotto, F.; Thomas, J.; Simeons, F.; Stojanovski, L.; Osuna-Cabello, M1; Brock, P.M.; Churcher, T.S.; Sala, K.A.; Zakutansky ,S.E.; Jiménez-Díaz, M.B.; Sanz, L.M; Riley, J.; Basak, R.; Campbell, M.; Avery, V.M.; Sauerwein, R.W.; Dechering, K.J.; Noviyanti, R.; Campo, B.; Frearson, J.A.; Angulo-Barturen, I.; Ferrer-Bazaga, S.; Gamo, F.J.; Wyatt, P.G.; Leroy, D.; Siegl, P.; Delves, M.J.; Kyle, D.E.; Wittlin, S.; Marfurt, J.; Price, R.N.; Sinden, R..; Winzeler, E.A.; Charman, S.A.; Bebrevska, L.; Gray, D.W.; Campbell, S.; Fairlamb, A.H.; Willis, P.A.; Rayner, J.C.; Fidock, D.A.; Read, K.D.; Gilbert, I.H. A novel multiplestage antimalarial agent that inhibits protein synthesis. Nature, 2015, 18;522(7556), 315-20.
Kato, N.; Comer, E.; Sakata-Kato, T.; Sharma, A.; Sharma, M.; Maetani, M.; Bastien, J.; Brancucci, N.M.; Bittker, J.A.; Corey, V.; Clarke, D.; Derbyshire, E.R.; Dornan, G.L.; Duffy, S.; Eckley, S.; Itoe, M.A.; Koolen, K.M.; Lewis, T.A.; Lui, P.S.; Lukens, A.K.; Lund, E.; March, S.; Meibalan, E.; Meier, B.C.; McPhail, J.A.; Mitasev, B.; Moss, E.L.; Sayes, M.; Van Gessel, Y.; Wawer, M.J.; Yoshinaga, T.; Zeeman, A.M.; Avery, V.M.; Bhatia, S.N.; Burke, J.E.; Catteruccia, F.; Clardy, J.C.; Clemons, P.A.; Dechering, K.J.; Duvall, J.R.; Foley, M.A.; Gusovsky, F.; Kocken, C.H.; Marti, M.; Morningstar, M.L.; Munoz, B.; Neafsey, D.E.; Sharma, A.; Winzeler, E.A.; Wirth, D.F.; Scherer, C.A.; Schreiber, S.L. Diversity-oriented synthesis yields novel multistage antimalarial inhibitors. Nature, 2016, 538(7625), 344-349.
[] [PMID: 27602946]
Izumiyama, S.; Omura, M.; Takasaki, T.; Ohmae, H.; Asahi, H. Plasmodium falciparum: development and validation of a measure of intraerythrocytic growth using SYBR Green I in a flow cytometer. Exp. Parasitol., 2009, 121(2), 144-150.
[] [PMID: 19017530]
Terstappen, G.C.; Schlüpen, C.; Raggiaschi, R.; Gaviraghi, G. Target deconvolution strategies in drug discovery. Nat. Rev. Drug Discov., 2007, 6(11), 891-903.
[] [PMID: 17917669]
Smith, C. Drug target validation: Hitting the target. Nature,, 2003, 422(6929), 341-347. 345 passim.
[] [PMID: 12646927]
Birkholtz, L.; van Brummelen, A.C.; Clark, K.; Niemand, J.; Maréchal, E.; Llinás, M.; Louw, A.I. Exploring functional genomics for drug target and therapeutics discovery in Plasmodia. Acta Trop., 2008, 105(2), 113-123.
[] [PMID: 18083131]
Sleno, L.; Emili, A. Proteomic methods for drug target discovery. Curr. Opin. Chem. Biol., 2008, 12(1), 46-54.
[] [PMID: 18282485]
Chan, X.W.; Wrenger, C.; Stahl, K.; Bergmann, B.; Winterberg, M.; Müller, I.B.; Saliba, K.J. Chemical and genetic validation of thiamine utilization as an antimalarial drug target. Nat. Commun., 2013, 4, 2060.
[] [PMID: 23804074]
Florens, L.; Washburn, M.P.; Raine, J.D.; Anthony, R.M.; Grainger, M.; Haynes, J.D.; Moch, J.K.; Muster, N.; Sacci, J.B.; Tabb, D.L.; Witney, A.A.; Wolters, D.; Wu, Y.; Gardner, M.J.; Holder, A.A.; Sinden, R.E.; Yates, J.R., III; Carucci, D.J. A proteomic view of the Plasmodium falciparum life cycle. Nature, 2002, 419(6906), 520-526.
[] [PMID: 12368866]
Veenstra, T.D. Proteomic approaches in drug discovery. Drug Discov. Today. Technol., 2006, 3, 433-440.
Amaya, M.; Baer, A.; Voss, K.; Campbell, C.; Mueller, C.; Bailey, C.; Kehn-Hall, K.; Petricoin, E., III; Narayanan, A. Proteomic strategies for the discovery of novel diagnostic and therapeutic targets for infectious diseases. Pathog. Dis., 2014, 71(2), 177-189.
[] [PMID: 24488789]
Bajorath, J. Integration of virtual and high-throughput screening. Nat. Rev. Drug Discov., 2002, 1(11), 882-894.
[] [PMID: 12415248]
Guido, R.V.C.; Oliva, G.; Montanari, C.A.; Andricopulo, A.D. Structural basis for selective inhibition of trypanosomatid glyceraldehyde-3-phosphate dehydrogenase: molecular docking and 3D QSAR studies. J. Chem. Inf. Model., 2008, 48(4), 918-929.
[] [PMID: 18303835]
Postigo, M.P.; Guido, R.V.; Oliva, G.; Castilho, M.S.; da Pitta, I.R.; de Albuquerque, J.F.; Andricopulo, A.D. Structural basis for selective inhibition of trypanosomatid glyceraldehyde-3-phosphate dehydrogenase: molecular docking and 3D QSAR studies. J. Chem. Inf. Model., 2010, 48(4), 918-929.
Maluf, F.V.; Andricopulo, A.D.; Oliva, G.; Guido, R.V.C. A pharmacophore-based virtual screening approach for the discovery of Trypanosoma cruzi GAPDH inhibitors. Future Med. Chem., 2013, 5(17), 2019-2035.
[] [PMID: 24215344]
Pauli, I.; dos Santos, R.N.; Rostirolla, D.C.; Martinelli, L.K.; Ducati, R.G.; Timmers, L.F.; Basso, L.A.; Santos, D.S.; Guido, R.V.; Andricopulo, A.D.; Norberto de Souza, O. Discovery of new inhibitors of Mycobacterium tuberculosis InhA enzyme using virtual screening and a 3Dpharmacophore- based approach. J. Chem. Inf. Model, 2013, 23 53(9), 2390-401.
Carballeira, N.M.; Bwalya, A.G.; Itoe, M.A.; Andricopulo, A.D.; Cordero-Maldonado, M.L.; Kaiser, M.; Mota, M.M.; Crawford, A.D.; Guido, R.V. Tasdemir. D. 2-Octadecynoic acid as a dual life stage inhibitor of Plasmodium infections and plasmodial FAS-II enzymes. Bioorg Med Chem Lett, 2014, 1;24(17), 4151-7.
Alves, E.; Maluf, F.V.; Bueno, V.B.; Guido, R.V.; Oliva, G.; Singh, M.; Scarpelli, P.; Costa, F.; Sartorello, R.; Catalani, L.H.; Brady, D.; Tewari, R.; Garcia, C.R. Biliverdin targets enolase and eukaryotic initiation factor 2 (eIF2α) to reduce the growth of intraerythrocytic development of the malaria parasite Plasmodium falciparum. Sci. Rep., 2016, 6(6), 22093.
[] [PMID: 26915471]
Guido, R.V.; Oliva, G. Structure-based drug discovery for tropical diseases. Curr. Top. Med. Chem., 2009, 9(9), 824-843.
[] [PMID: 19754397]
Guido, R.V.; Oliva, G.; Andricopulo, A.D. Modern drug discovery technologies: opportunities and challenges in lead discovery. Comb. Chem. High Throughput Screen., 2011, 14(10), 830-839.
[] [PMID: 21843147]
Ferreira, R.S.; Guido, R.V.C.; Andricopulo, A.D.; Oliva, G. In silico screening strategies for novel inhibitors of parasitic diseases. Expert Opin. Drug Discov., 2011, 6(5), 481-489.
[] [PMID: 22646074]
Hol, W.G.J. Three-dimensional structures in the design of therapeutics targeting parasitic protozoa: reflections on the past, present and future. Acta Crystallogr. F Struct. Biol. Commun., 2015, 71(Pt 5), 485-499.
[] [PMID: 25945701]
Renaud, J.P.; Chung, C.W.; Danielson, U.H.; Egner, U.; Hennig, M.; Hubbard, R.E.; Nar, H. Biophysics in drug discovery: impact, challenges and opportunities. Nat. Rev. Drug Discov., 2016, 15(10), 679-698.
[] [PMID: 27516170]
Mehlin, C.; Boni, E.; Buckner, F.S.; Engel, L.; Feist, T.; Gelb, M.H.; Haji, L.; Kim, D.; Liu, C.; Mueller, N.; Myler, P.J.; Reddy, J.T.; Sampson, J.N.; Subramanian, E.; Van Voorhis, W.C.; Worthey, E.; Zucker, F.; Hol, W.G. Heterologous expression of proteins from Plasmodium falciparum: results from 1000 genes. Mol. Biochem. Parasitol., 2006, 148(2), 144-160.
[] [PMID: 16644028]
Brady, R.L.; Cameron, A. Structure-based approaches to the development of novel anti-malarials. Curr. Drug Targets, 2004, 5(2), 137-149.
[] [PMID: 15011947]
Lepre, C.A. Library design for NMR-based screening. Drug Discov. Today, 2001, 6(3), 133-140.
[] [PMID: 11165186]
Pellecchia, M.; Meininger, D.; Dong, Q.; Chang, E.; Jack, R.; Sem, D.S. NMR-based structural characterization of large protein-ligand interactions. J. Biomol. NMR, 2002, 22(2), 165-173.
[] [PMID: 11883777]
Náray-Szabó, G.; Perczel, A. Protein structure and dynamics. Int. J. Terraspace Sci. Engineer., 2014, 6, 7-16.
Neumann, T.; Junker, H-D.; Schmidt, K.; Sekul, R. SPR-based fragment screening: advantages and applications. Curr. Top. Med. Chem., 2007, 7(16), 1630-1642.
[] [PMID: 17979772]
Leavitt, S.; Freire, E. Direct measurement of protein binding energetics by isothermal titration calorimetry. Curr. Opin. Struct. Biol., 2001, 11(5), 560-566.
[] [PMID: 11785756]
Falconer, R.J.; Collins, B.M. Survey of the year 2009: applications of isothermal titration calorimetry. J. Mol. Recognit., 2011, 24(1), 1-16.
[] [PMID: 21157775]
Seidel, S.A.I.; Dijkman, P.M.; Lea, W.A.; van den Bogaart, G.; Jerabek-Willemsen, M.; Lazic, A.; Joseph, J.S.; Srinivasan, P.; Baaske, P.; Simeonov, A.; Katritch, I.; Melo, F.A.; Ladbury, J.E.; Schreiber, G.; Watts, A.; Braun, D.; Duhr, S. Microscale thermophoresis quantifies biomolecular interactions under previously challenging conditions. Methods, 2013, 59(3), 301-315.
[] [PMID: 23270813]
de Sousa, L.R.; Wu, H.; Nebo, L.; Fernandes, J.B.; da Silva, M.F.; Kiefer, W.; Kanitz, M.; Bodem, J.; Diederich, W.E.; Schirmeister, T.; Vieira, P.C. Flavonoids as noncompetitive inhibitors of Dengue virus NS2B-NS3 protease: inhibition kinetics and docking studies. Bioorg. Med. Chem., 2015, 23(3), 466-470.
[] [PMID: 25564380]
Jerabek-Willemsen, M.; André, T.; Wanner, R.; Roth, H.M.; Duhr, S.; Baaske, P.; Breitsprecher, D. MicroScale; Thermophoresis. Interaction analysis and beyond. J. Mol. Struct., 2014, 1077, 101-113.
Gossas, T.; Nordström, H.; Xu, M-H.; Sun, Z-H.; Lin, G-Q.; Wallberg, H.; Danielsno, U.H. The advantage of biosensor analysis over enzyme inhibition studies for slow dissociating inhibitors-characterization of hydroxamate-based matrix metalloproteinase-12 inhibitors. MedChemComm, 2013, 4, 432-442.
Aguiar, A.C.; Rocha, E.M.; Souza, N.B.; França, T.C.; Krettli, A.U. New approaches in antimalarial drug discovery and development: a review. Mem. Inst. Oswaldo Cruz, 2012, 107(7), 831-845.
[] [PMID: 23147137]

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