Clotrimazole scaffold as an innovative pharmacophore towards potent antimalarial agents: Design, synthesis, and biological and structure-activity relationship studies

Journal of Medicinal Chemistry

Volumn 51, Issue 5, 2008, Pages 1278-1294

  Gemma, Sandra ^a   Campiani, Giuseppe ^a   Butini, Stefania ^a   Kukreja, Gagan ^a   Coccone, Salvatore Sanna ^a   Joshi, Bhupendra P ^a   Persico, Marco ^a,b   Nacci, Vito ^a   Fiorini, Isabella ^a   Novellino, Ettore ^a,b   Fattorusso, Ernesto ^a,b   Taglialatela Scafati, Orazio ^a,b   Savini, Luisa ^a   Taramelli, Donatella ^a,c   Basilico, Nicoletta ^a,d   Parapini, Silvia ^a,c   Morace, Giulia ^c   Yardley, Vanessa ^a,d   Croft, Simon ^a,d   Coletta, Massimiliano ^c   Marini, Stefano ^d   Fattorusso, Caterina ^a,b   more..

^a UNIVERSITY OF SIENA   (Italy)

^b UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^c UNIVERSITY OF MILAN   (Italy)

^d UNIVERSITY OF ROME TOR VERGATA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CHLOROQUINE; CLOTRIMAZOLE; CYTOCHROME P450; HEMATIN; HEME; STEROL 14ALPHA DEMETHYLASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIMALARIAL ACTIVITY; ARTICLE; CELL LINE; CONTROLLED STUDY; COST BENEFIT ANALYSIS; DRUG DESIGN; DRUG SYNTHESIS; FEMALE; MALARIA; MATRIX ATTACHMENT REGION; MOUSE; NONHUMAN; PHARMACOPHORE; PLASMODIUM CHABAUDI; STRUCTURE ACTIVITY RELATION; TOXICITY;

ANIMALS; ANTIFUNGAL AGENTS; ANTIMALARIALS; CELL LINE; CLOTRIMAZOLE; CYTOCHROME P-450 ENZYME SYSTEM; DRUG DESIGN; FEMALE; FERRIC COMPOUNDS; HEME; HUMANS; MICE; MODELS, MOLECULAR; OXIDOREDUCTASES; PARASITIC SENSITIVITY TESTS; PLASMODIUM BERGHEI; PLASMODIUM CHABAUDI; PLASMODIUM FALCIPARUM; PROTOPORPHYRINS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 41649106230     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm701247k     Document Type: Article

References (51)

1. Hay, S. I.; Guerra, C. A.; Tatem, A. J.; Noor, A. M.; Snow, R. W. The global distribution and population at risk of malaria: past, present, and future. Lancet Infect. Dis. 2004, 4, 327-336.
2. (a) Beckera, K.; Tilley, L.; Vennerstrom, J. L.; Roberts, D.; Rogerson, S.; Ginsburg, H. Oxidative stress in malaria parasite-infected erythrocytes: host-parasite interactions. Int. J. Parasitol. 2004, 34, 163-189.
3. (b) Müller, S. Redox and antioxidant systems of the malaria parasite Plasmodium falciparum. Mol. Microbiol. 2004, 53, 1291-1305.
4. (a) Fitch, C. D. Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs. Life Sci. 2004, 74, 1957-1972.
5. (b) Homewood, C. A.; Moore, G. A.; Warhurst, D. C.; Atkinson, E. M. Purification and some properties of malarial pigment. Annals Trop. Med. Parasitol. 1975, 69, 283-287.
6. (c) Slater, A. F. G.; Swiggard, W. J.; Orton, B. R.; Flitter, W. D.; Goldberg, D. E.; Cerami, A.; Henderson, G. B. An iron-carboxylate bond links the heme units of malaria pigment. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 325-329.
7. (d) Pagola, S.; Stephens, P. W.; Bohle, S. D.; D. Kosar, A. D.; Madsen, S. K. The structure of malaria pigment β-haematin. Nature 2000, 404, 307-310.
8. (e) Ginsburg, H.; Famin, O.; Zhang, J.; Krugliak, M. Inhibition of glutathione-dependent degradation of heme by chloroquine and amodiaquine as a possible basis for their antimalarial mode of action. Biochem. Pharmacol. 1998, 56, 1305-1313.
9. (f) Famin, O.; Krugliak, M.; Ginsburg, H. Kinetics of inhibition of glutathione-mediated degradation of ferriprotoporphyrin IX by antimalarial drugs. Biochem. Pharmacol. 1999, 58, 59-68.
10. (a) Towie, N. Malaria breakthrough raises spectre of drug resistance. Nature 2006, 440, 452-453.
11. 2+ ATPase), tctp, mdr1, and cg10. Antimicrob. Agents Chemother. 2006, 50, 480-489.
12. (a) Gemma, S.; Kukreja, G.; Campiani, G.; Butini, S.; Bemetti, M.; Joshi, B. P.; Savini, L.; Basilico, N.; Taramelli, D.; Yardley, V.; Bertamino, A.; Novellino, E.; Persico, M.; Catalanotti, B.; Fattorusso, C. Development of piperazine-tethered heterodimers as potent antimalarials against chloroquine-resistant P. falciparum strains. Synthesis and molecular modelling. Bioorg. Med. Chem. Lett. 2007, 17, 3535-3539.
13. (b) Gemma, S.; Kukreja, G.; Fattorusso, C.; Persico, M.; Romano, M. P.; Altarelli, M.; Savini, L.; Campiani, G.; Fattorusso, E.; Basilico, N.; Taramelli, D.; Yardley, V.; Butini, S. Synthesis of N1-arylidene-N2-quinolyl- and N2-acrydinylhydrazones as potent antimalarial agents active against CQ-resistant P. falciparum strains. Bioorg. Med. Chem. Lett. 2006, 16, 5384-5388.
14. (c) Fattorusso, C.; Campiani, G.; Catalanotti, B.; Persico, M.; Basilico, N.; Parapini, S.; Taramelli, D.; Campagnuolo, C.; Fattorusso, E.; Romano, A.; Taglialatela-Scafati, O. Endoperoxide derivatives from marine organisms: 1,2-dioxanes of the plakortin family as novel antimalarial agents. J. Med. Chem. 2006, 49, 7088-7094.
15. Gemma, S.; Campiani, G.; Butini, S.; Kukreja, G.; Joshi, B. P.; Persico, M.; Catalanotti, B.; Novellino, E.; Fattorusso, E.; Nacci, V.; Savini, L.; Taramelli, D.; Basilico, N.; Morace, G.; Yardley, V.; Fattorusso, C. Design and synthesis of potent antimalarial agents based on clotrimazole scaffold: Exploring an innovative pharmacophore. J. Med. Chem. 2007, 50, 595-598.
16. Tiffert, T.; Ginsburg, H.; Krugliak, M.; Elford, B. C.; Lew, V. L. Potent antimalarial activity of clotrimazole in in vitro cultures of Plasmodium falciparum. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 331-336.
17. Saliba, K. J.; Kirk, K. Clotrimazole inhibits the growth of Plasmodium falciparum in vitro. Trans. R. Soc. Trop. Med. Hyg. 1998, 92, 666-667.
18. Trivedi, V.; Chand, P.; Srivastava, K.; Puri, S. K.; Maulik, P. R.; Bandyopadhyay, U. Clotrimazole inhibits hemoperoxidase of Plasmodium falciparum and induces oxidative stress. J. Biol. Chem. 2005, 280, 41129-41136.
19. Chong, C. R.; Sullivan, D. J., Jr. Inhibition of heme crystal growth by antimalarials and other compounds: Implications for drug discovery. Biochem. Pharmacol. 2003, 66, 2201-2212.
20. Huy, N. T.; Kamei, K.; Yamamoto, T.; Kondo, Y.; Kanaori, K.; Takano, R.; Tajima, K.; Hara, S. Clotrimazole binds to heme and enhances heme-dependent hemolysis. J. Biol. Chem. 2002, 277, 4152-4158.
21. Eaton, D. R.; Wilson, K. M. Reaction of imidazole and hydroquinone with oxymyoglobin. J. Inorg. Biochem. 1979, 10, 195-203.
22. Eaton, D. R.; Wilkins, R. G. Reduction by dithionite ion of adducts of metmyoglobin with imidazole, pyridine, and derivatives. J. Biol. Chem. 1978, 253, 908-915.
23. Hicks, R. G. What's new in stable radical chemistry? Org. Biomol. Chem. 2007, 5, 1321-1338.
24. Short, J. H. Formation of Grignard reagents from 3-bromo-N,N-dimethylbenzylamine and 4-bromo-N,N-diethylbenzylamine and their reactions with benzaldehyde. J. Chem. Soc. C 1966, 313-315.
25. Thorsett, E. D.; Stermitz, F. R. Alkylation of haloquinolines by Grignard reagents with nickel-phosphine complex catalysts. J. Heterocycl. Chem. 1973, 10, 243-244.
26. Slama, J. T.; Hancock, J. L.; Rho, T.; Sambucetti, L.; Bachmann, K. A. Influence of some novel N-substituted azoles and pyridines on rat hepatic CYP3A activity. Biochem. Pharmacol. 1998, 55, 1881-1892.
27. Heindel, N. D.; Fine, S. A. Acid-catalyzed alcoholysis of 4,7-dichloroquinoline. J. Heterocycl. Chem. 1969, 6, 961.
28. Yamanaka, H.; Ohba, S. Reaction of methoxy-N-heteroarmatics with phenylacetonitrile under basic conditions. Heterocycles 1990, 31, 895-909.
29. Da Silva, G.; Moore, E. E.; Bozzelli, J. W. Quantum chemical study of the structure and thermochemistry of the five-membered nitrogen-containing hetrocycles and their anions and radicals. J. Phys. Chem. A 2006, 110, 13979-13988.
30. Inbaraj, J.; Bilski, P.; Chignell, C. F. Photophysical and photochemical studies of 2-phenylbenzimidazole and UVB sunscreen 2-phenylbenzimidazole-5- sulfonic acid. Photochem. Photobiol. 2002, 75, 107-116.
31. Mabeza, G. F.; Loyevsky, M.; Gordeuk, V. R.; Weiss, G. Iron chelation therapy for malaria: A review. Pharmacol. Ther. 1999, 81, 53-75.
32. (a) O'Neill, P. M.; Ward, S. A.; Berry, N. G.; Jeyadevan, J. P.; Biagini, G. A.; Asadollaly, E.; Park, B. K.; Bray, P. G. A medicinal chemistry perspective on 4-aminoquinoline antimalarial drugs. Curr. Top. Med. Chem. 2006, 6, 479-507.
33. (b) Sparatore, A.; Basilico, N.; Parapini, S.; Romeo, S.; Novelli, F.; Sparatore, F.; Taramelli, D. 4-Aminoquinoline quinolizidinyl- and quinolizidinylalkyl- derivatives with antimalarial activity. Bioorg. Med. Chem. 2005, 13, 5338-5345.
34. Ursos, L. M. B.; Roepe, P. D. Chloroquine resistance in the malarial parasite, Plasmodium falciparum. Med. Res. Rev. 2002, 22, 465-491.
35. Parapini, S.; Basilico, N.; Pasini, E.; Egan, T. J.; Olliaro, P.; Taramelli, D.; Monti, D. Standardization of the physicochemical parameters to assess in vitro the β-hematin inhibitory activity of antimalarial drugs. Exp. Parasitol. 2000, 96, 249-256.
36. Holtje, H. D.; Fattorusso, C. Construction of a model of the Candida albicans lanosterol 14-alpha-demethylase active site using the homology modelling technique. Pharm. Acta Helv. 1998, 72, 271-277.
37. Winn, P. J.; Ludemann, S. K.; Gauges, R.; Lounnas, V.; Wade, R. C. Comparison of the dynamics of substrate access channels in three cytochrome P450s reveals different opening mechanisms and a novel functional role for a buried arginine. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 5361-5366.
38. (a) D'Atri, S.; Tentori, L.; Fuggetta, M. P.; Marini, S.; Bonmassar, E. A miniaturized cell-mediated cytotoxicity assay with human effector mononuclear cells. Int. J. Tissue React. 1986, 8, 383-390.
39. (b) Scatena, R.; Marini, S.; Tavazzi, B.; Lazzarino, G.; Giardina, B. Sterol metabolism and lymphocyte function: measure of relative LDL receptor number by peripheral blood lymphocytes activation. Clin. Chem. Enzymol. Commun. 1990, 3, 73-79.
40. Peters, W.; Robinson, B. L. In Handbook of Animal Models of Infection; Zak., O., Sande, M., Eds.; Academic: London, 1999; pp 757-773.
41. Short, J. H. Formation of Grignard reagents from 3-bromo-N,N-dimethyl-benzylamine and 4-bromo-N,N-diethylbenzylamine and their reactions with benzaldehyde. J. Chem. Soc. C 1966, 3, 313-315.
42. Bender, D. R.; Coffen, D. L. Synthetic quinine analogs. V. Quinolinemethanols related to desvinylquinine. J. Heterocycl. Chem. 1971, 8, 937-942.
43. Maple, J. R.; Hwang, M. J.; Stockfisch, T. P.; Dinur, U; Waldman, M.; Ewig, C. S.; Hagler, A. T. Derivation of class II force fields. I. Methodology and quantum force field for the alkyl functional group and alkane molecules. J. Comput. Chem. 1994, 15, 162-182.
44. Dewar, M. J. S.; Thiel, W. Ground states of molecules. 38. The MNDO method. Approximations and parameters. J. Am. Chem. Soc. 1977, 99, 4899-4907.
45. Fletcher, R. Unconstrained Optimization. In Pratical Methods of Optimization; John Wiley & Sons: New York, 1980; Vol. 1.
46. Stewart, J. J. P. MOPAC: a semiempirical molecular orbital program. J. Comput.-Aided Mol. Des. 1990, 4, 1-105.
47. Senderowitz, H.; Guarnieri, F.; Still, W. C. A smart Monte Carlo technique for free energy simulations of multiconformational molecules. Direct calculations of the conformational populations of organic molecules. J. Am. Chem. Soc. 1995, 117, 8211-8219.
48. Ding, H. Q.; Karasawa, N.; Goddard, W. A., III. Atomic level simulations on a million particles: The cell multipole method for Coulomb and London non-bond interactions. J. Chem. Phys. 1992, 97, 4309-4315.
49. Trager, W.; Jensen, J. B. Human malaria parasites in continuous culture. Science 1976, 193, 673-675.
50. Makler, M.; Hinrichs, D. Measurement of the lactate dehydrogenase activity of Plasmodium falciparum as an assessment of parasitemia. Am. J. Trop. Med. Hyg. 1993, 48, 205-210.
51. Desjardins, R. E.; Canfiled, C. J.; Haynes, J. D.; Chulay, J. D. Quanititative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob. Agents Chemother. 1979, 16, 710-718.