Back to the future: Lessons learned in modern target-based and whole-cell lead optimization of antimalarials

Current Topics in Medicinal Chemistry

Volumn 12, Issue 5, 2012, Pages 473-483

  Chatterjee, Arnab K ^a   Yeung, Bryan K S ^b  

^a GENOMICS INSTITUTE OF THE NOVARTIS RESEARCH FOUNDATION   (United States)

^b NOVARTIS INSTITUTE FOR TROPICAL DISEASES   (Singapore)

Author keywords

Imidazolopiperazines; Lead optimization; Malaria; Spiroindolones; Whole cell screening

Indexed keywords

ANTIMALARIAL AGENT; ARTESUNATE; BENZAMIDE DERIVATIVE; CHLOROQUINE; CYCLOGUANIL; DIHYDROFOLATE REDUCTASE; IMIDAZOLOPIPERAZINE DERIVATIVE; IMIDAZOLOPYRIMIDINE DERIVATIVE; PURFALCAMINE; PYRIMETHAMINE; QN 254; SPIROINDOLE DERIVATIVE; UNCLASSIFIED DRUG;

CELL SCREENING; DRUG BINDING; DRUG DOSE INCREASE; DRUG POTENCY; DRUG SELECTIVITY; DRUG TARGETING; HUMAN; NONHUMAN; PLASMODIUM BERGHEI INFECTION; PLASMODIUM FALCIPARUM; PROCESS OPTIMIZATION; REVIEW;

ANTIMALARIALS; DRUG DISCOVERY; HUMANS; MOLECULAR TARGETED THERAPY;

EID: 84857734006     PISSN: 15680266     EISSN: 18734294     Source Type: Journal    
DOI: 10.2174/156802612799362977     Document Type: Review

References (30)

1. Gamo, F.-J.; Sanz, L. M.; Vidal, J.; de Cozar, C.; Alvarez, E.; Lavandera, J.-L.; Vanderwall, D. E.; Green, D. V. S.; Kumar, V, Hasan, S.; Brown, J. R.; Peishoff, C. E.; Cardon, L. R.; Garcia-Bustos, J. F. Thousands of chemical starting points for antimalarial lead identification. Nature, 2010, 465, 305-310.
2. Guiguemde, W. A.; Shelat, A. A.; Bouck, D.; Duffy, S.; Crowther, G. J.; Davis, P. H.; Smithson, D. C.; Connelly, M.; Clark, J.; Zhu, F.; Jimenez-Diaz, M. B.; Martinez, M. S.; Wilson, E. B.; Tripathi, A. K.; Gut, J.; Sharlow, E. R., Bathurst, I.; El Mazouni, F.; Fowble, J. W.; Forquer, I.; McGinley, P. L.; Castro, S.; Angulo-Barturen, I.; Ferrer, S.; Rosenthal, P. J.; de Risi, J. L.; Sullivan Jr. D. J.; Lazo, J. S.; Roos, D. S.; Riscoe, M. K.; Phillips, M. A.; Rathod, P. K.; van Voorhis, W. C.; Avery, V. M.; Guy, R. K. Chemical genetics of Plasmodium falciparum. Nature, 2010, 465, 311-315.
3. McNamara, C.; Winzeler, E. A. Target identification and validation of novel antimalarials. Future Microbiol., 2011, 6, 693-704.
4. Nzila, A. The past, present, and future of antifolates in the treatment of Plasmodium falciparum infection. J. Antimicrob. Chemother., 2006, 57, 1043-1054.
5. Nzila, A.; Rottmann, M.; Chitnumsub, P.; Kiara, S. M.; Kamchonwongpaisan, S.; Maneeruttanarungroj, C.; Taweechai, S.; Yeung, B. K. S.; Goh, A.; Lakshminarayana, S. B.; Zou, B.; Wong, J.; Ma, N. L.; Weaver, M.; Thomas H. Keller, T. H.; Dartois, V.; Wittlin, S.; Brun, R.; Yuthavong, Y.; Diagana, T. T. Preclinical evaluation of the antifolate QN254, 5-Chloro-N'6'-(2,5 di-methoxy-benzyl)-quinazoline-2,4,6-triamine, as an antimalarial drug candidate. Antimicrob. Agents Chemother., 2010, 54, 2603-2610.
6. Canfield, C. J.; Milhous, W. K.; Ager, A. L.; Rossan, R. N.; Sweeney, T. R. Lewis, N. J.; Jacobus D. P. PS-15: a potent, orally active antimalarial from a new class of folic acid antagonists. Am. J. Trop. Med. Hyg., 1993, 49, 121-126.
7. Winstanley, P. A.; Mberu, E. K.; Szwandt, I. S.; Breckenridge, A. M.; Watkins W. M. In vitro activities of novel antifolate drug combinations against Plasmodium falciparum and human granulocyte CFUs. Antimicrob. Agents Chemother., 1995, 39, 948-952.
8. Kato, N.; Sakata, T.; Breton, G.; Le Roch, K. G.; Nagle, A.; Andersen, C.; Bursulaya, B.; Henson, K.; Johnson, J.; Kumar, K. A.; Marr, F.; Mason, D.; McNamara, C.; Plouffe, D.; Ramachandran, V.; Spooner, M.; Tuntland, T.; Zhou, Y.; Peters, E. C.; Chatterjee, A.; Schultz, P. G.; Ward, G. E.; Gray, N.; Harper, J.; Winzeler, E. A. Gene expression signatures and small-molecule compounds link a protein kinase to Plasmodium falciparum motility. Nat. Chem. Biol., 2008, 4, 347-356.
9. Ding, S.; Gray, N.S.; Wu, X.; Ding, Q; Schultz, P.G. A combinatorial scaffold approach toward kinase-directed heterocycle libraries. J. Am. Chem. Soc., 2002, 124, 1594-1596.
10. Meijer, L.; Raymond, E. Roscovitine and other purines as kinase inhibitors. from starfish oocytes to clinical trials. Acc. Chem. Res., 2003, 36, 417-425.
11. Medicines for Malaria Ventures (MMV) website. Available on www.mmv.org
12. Payne, D. J.; Gwynn, M. N.; Holmes, D. J.; Pompliano, D. L. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat. Rev. Drug Discov., 2007, 6, 29-40.
13. 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.; Jimenez-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, 5540-5561.
14. Plouffe, D.; Brinker, A.; McNamara, C.; Henson, K.; Kato, N.; Kuhen, K.; Nagle, A.; Adrian, F.; Matzen, J. T.; Anderson, P.; Nam, T. G.; Gray, N. S.; Chatterjee, A.; Janes, J.; Yan, S. F.; Trager, R.; Caldwell, J. S.; Schultz, P. G.; Zhou, Y.; Winzeler, E. A. In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen. Proc. Natl. Acad. Sci. USA, 2008, 105, 9059-9064.
15. EBI database. Available at https://www.ebi.ac.uk/chembldb/.
16. Tanaka, D.; Tsuda, Y.; Shiyama, T.; Nishimura, T.; Chiyo, N.; Tominaga, Y.; Sawada, N.; Mimoto, T.; Kusunose, N. A practical use of ligand efficiency indices out of the fragment-based approach: Ligand efficiency-guided lead identification of soluble epoxide hydrolase inhibitors. J. Med. Chem., 2011, 54, 851-857.
17. Reynolds, C. H.; Holloway, M. K. Thermodynamics of ligand binding and efficiency. Med. Chem. Lett., 2011, 2, 433-437.
18. Ren, P.; Wang, X.; Zhang, G.; Ding, Q.; You, S.; Zhang, Q.; Chopiuk, G.; Albaugh, P. A.; Sim, T.; Gray, N. S. WO 2005123719; Chem. Abstr., 2005, 144, 88305.
19. Melnick, J. S.; Janes, J.; Kim, S.; Chang, J. Y.; Sipes, D. G.; Gunderson, D.; Jarnes, L.; Matzen, J. T.; Garcia, M. E.; Hood, T. L.; Beigi, R.; Xia, G.; Harig, R. A.; Asatryan, H.; Yan, S. F.; Zhou, Y.; Gu, X.; Saadat, A.; Zhou, V.; King, F. J.; Shaw, C. M.; Su, A. I.; Downs, R.; Gray, N. S.; Schultz, P. G.; Warmuth, M.; Caldwell, J. S. An efficient rapid system for profiling the cellular activities of molecular libraries. Proc. Natl. Acad. Sci. USA, 2006, 103, 3153-3158.
20. Wu, T.; Nagle, A.; Sakata, T.; Henson, K.; Borboa, R.; Chen, Z.; Kuhen, K.; Plouffe, D.; Winzeler, E.; Adrian, F.; Tuntland, T.; Chang, J.; Simerson, S.; Howard, S.; Ek, J.; Isbell, J.; Deng, X.; Gray, N. S.; Tully, D. C.; Chatterjee, A. K. Cell-based optimization of novel benzamides as potential antimalarial leads. Bioorg. Med. Chem. Lett., 2009, 19, 6970-6974.
21. Deng, X.; Nagle, A.; Wu, T.; Sakata, T.; Henson, K.; Chen, Z.; Kuhen, K.; Plouffe, D.; Winzeler, E.; Adrian, F.; Tuntland, T.; Chang, J.; Simerson, S.; Howard, S.; Ek, J.; Isbell, J.; Tully, D. C.; Chatterjee, A. K.; Gray, N. S. Discovery of novel 1H-imidazol-2- yl-pyrimidine-4,6-diamines as potential antimalarials. Bioorg. Med. Chem. Lett., 2010, 20, 4027-4031.
22. Aronov, A. M. Predictive in silico modeling for hERG channel blockers. Drug Discov. Today, 2005, 10, 149-155.
23. Wu, T.; Nagle, A.; Kuhen, K.; Gagaring, K.; Borboa, R.; Francek, C.; Chen, Z.; Plouffe, D.; Goh, A.; Lakshminarayana, S. B.; Wu, J.; Ang, H. Q.; Zeng, P.; Kang, M. L.; Tan, W.; Tan, M.; Ye, N.; Lin, X.; Caldwell, C.; Ek, J.; Skolnik, S.; Liu, F.; Wang, J.; Chang, J.; Li, C.; Hollenbeck, T.; Tuntland, T.; Isbell, J.; Fischli, C.; Brun, R.; Rottmann, M.; Dartois, V.; Keller, T.; Diagana, T.; Winzeler, E.; Glynne, R.; Tully, D. C.; Chatterjee, A. K. Imidazolopiperazines: hit to lead optimization of new antimalarial agents. J. Med. Chem., 2011, 54, 5116-5130.
24. Lee, A. J.; Zhu, B. T. NADPH-dependent formation of polar and nonpolar estrogen metabolites following incubations of 17 betaestradiol with human liver microsomes. Drug Metab. Dispos., 2004, 32, 876-883.
25. Tuntland, T.; Liu, B.; Chang, J.; Gordon, W. P.; Isbell, J.; Zhou, Y. Snapshot PK: a rapid rodent in vivo preclinical screening approach. Drug Discov. Today 2008, 13, 360-367.
26. Fidock, D. A.; Rosenthal, P. J.; Croft, S. L.; Brun, R.; Nwaka, S. Antimalarial drug discovery: efficacy models for compound screening. Nat. Rev. Drug Discov., 2004, 3, 509-520.
27. Wells, T. N. C. Natural products as starting points for future antimalarial therapies: going back to our roots? Malaria J., 2011, 10, S3.
28. Yeung, B. K. S.; Zou, B.; Rottmann, M.; Lakshminarayana, S. B.; Ang, S. H.; Leong, S. H.; Tan, J.; Wong, J.; Keller-Maerki, S.; Fischli, C.; Goh, A.; Schmitt, E. K.; Krastel, P.; Francotte, E.; Kuhen, K.; Plouffe, A.; Henson, K.; Wagner, T.; Winzeler, E. A.; Petersen, F.; Brun, R.; Dartois, V.; Diagana, T. T. and Keller, T. H. Spirotetrahydro β-carbolines (spiroindolones): A new class of potent and orally efficacious compounds for the treatment of Malar. J. Med. Chem., 2010, 53, 5155-5164.
29. Rottmann, M.; McNamara, C.; Yeung, B. K. S.; Lee, M. C. S.; Zou, B.; Russell, B.; Seitz, P.; Plouffe, D. M.; Dharia, N. V.; Tan, J.; Cohen, S. B.; Spencer, K. R.; González-Páez, G. E.; Lakshminarayana, S. B.; Goh, A.; Suwanarusk, R.; Jegla, T.; Schmitt, E. K.; Beck, H.-P.; Brun, R.; Nosten, F.; Renia, L.; Dartois, V.; Keller, T. H.; Fidock, D. A.; Winzeler, E. A.; Diagana, T.T. Spiroindolones, a potent compound class for the treatment of malaria. Science, 2010, 329, 1175-1180.
30. Grigoryan, N.P.; Pogosyan, S.A.; Paronikyan, R.G. Synthesis and antispasmodic activity of spiro[b-carbolineindolones] and spiro[indoleindolo[2,3-c]azepinones]. Armenian Chem. J., 2005, 58, 101-104.