Chitin synthase inhibitors as antifungal agents

Mini-Reviews in Medicinal Chemistry

Volumn 13, Issue 2, 2013, Pages 222-236

  Chaudhary, Preeti M ^a   Tupe, Santosh G ^a   Deshpande, Mukund V ^a  

^a NATIONAL CHEMICAL LABORATORY   (India)

Author keywords

Antifungal agents; Chitin synthase; Chitin synthase inhibitors; Nikkomycin; Peptidyl nucleoside antibiotics; Polyoxin

Indexed keywords

AMPHOTERICIN B; ANIDULAFUNGIN; ANTIFUNGAL AGENT; CASPOFUNGIN; CHALCONE DERIVATIVE; CHITIN SYNTHASE; CHITIN SYNTHASE INHIBITOR; FLUCONAZOLE; FLUCYTOSINE; IMIDAZOLE DERIVATIVE; ITRACONAZOLE; NIKKOMYCIN Z; NYSTATIN; POLYOXIN; POLYOXIN D; TERBINAFINE; TRIAZOLE DERIVATIVE; UNCLASSIFIED DRUG; VORICONAZOLE;

AMINO ACID SEQUENCE; ANTIFUNGAL ACTIVITY; ARTICLE; CHEMICAL MODIFICATION; DRUG ISOLATION; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; FUNGAL CELL CULTURE; HUMAN; NONHUMAN; STREPTOMYCES;

EID: 84875463788     PISSN: 13895575     EISSN: 18755607     Source Type: Journal    
DOI: 10.2174/1389557511313020005     Document Type: Article

References (101)

1. Maertens, J.; Vrebos, M.; Boogaerts, M. Assessing risk factors for systemic fungal infections. Eur. J. Cancer Care (Engl.) 2001, 10, 56-62.
2. Richardson, M.D. Changing patterns and trends in systemic fungal infections. J. Antimicrob. Chemother., 2005, 56, i5-i11.
3. Richardson, M.; Lass-Flörl, C. Changing epidemiology of systemic fungal infections. Clin. Microbiol. Infect., 2008, 14, 5-24.
4. Lass-Flörl, C. The changing face of epidemiology of invasive fungal disease in Europe. Mycoses, 2009, 52, 197-205.
5. Walsh, T.J.; Groll, A.H. Emerging fungal pathogens: evolving challenges to immunocompromised patients for the twenty-first century. Transpl. Infect. Dis., 1999, 1, 247-261.
6. Nucci, M.; Marr, K.A. Emerging fungal diseases. Clin. Infect. Dis., 2005, 41, 521-526.
7. Walsh, T.J.; Groll, A.; Hiemenz, J.; Fleming, R.; Roilides, E.; Anaissie, E. Infections due to emerging and uncommon medically important fungal pathogens. Clin. Microbiol. Infect., 2004, 10, 48-66.
8. Pfaller, M.A.; Diekema, D.J. Rare and emerging opportunistic fungal pathogens: concern for resistance beyond Candida albicans and Aspergillus fumigatus. J. Clin. Microbiol., 2004, 42, 4419-4431.
9. Eliopoulos, G.M.; Perea, S.; Patterson, T.F. Antifungal resistance in pathogenic fungi. Clin. Infect. Dis., 2002, 35, 1073-1080.
10. Shao, P.-L.; Huang, L.-M.; Hsueh, P.-R. Recent advances and challenges in the treatment of invasive fungal infections. Int. J. Antimicrob. Agents, 2007, 30, 487-495.
11. Petrikkos, G.; Skiada, A. Recent advances in antifungal chemotherapy. Int. J. Antimicrob. Agents, 2007, 30, 108-117.
12. Ostrosky-Zeichner, L.; Casadevall, A.; Galgiani, J.N.; Odds, F.C.; Rex, J.H. An insight into the antifungal pipeline: selected new molecules and beyond. Nat. Rev. Drug Discov., 2010, 9, 719-727.
13. Vatmurge, N.S.; Hazra, B.G.; Pore, V.S.; Shirazi, F.; Chavan, P.S.; Deshpande, M.V. Synthesis and antimicrobial activity of beta-lactam-bile acid conjugates linked via triazole. Bioorg. Med. Chem. Lett., 2008, 18, 2043-2047.
14. Bavikar, S.N.; Salunke, D.B.; Hazra, B.G.; Pore, V.S.; Dodd, R.H.; Thierry, J.; Shirazi, F.; Deshpande, M.V.; Kadreppa, S.; Chattopadhyay, S. Synthesis of chimeric tetrapeptide-linked cholic acid derivatives: Impending synergistic agents. Bioorg. Med. Chem. Lett., 2008, 18, 5512-5517.
15. Vatmurge, N.S.; Hazra, B.G.; Pore, V.S.; Shirazi, F.; Deshpande, M.V.; Kadreppa, S.; Chattopadhyay, S.; Gonnade, R.G. Synthesis and biological evaluation of bile acid dimers linked with 1,2,3-triazole and bis-beta-lactam. Org. Biomol. Chem., 2008, 6, 3823-3830.
16. Ruiz-Herrera, J.; San-Blas, G. Chitin synthesis as a target for antifungal drugs. Curr. Drug Targets Infect. Disord., 2003, 3, 77-91.
17. Bartnicki-Garcia, S. Chitosomes: past, present and future. FEMS Yeast Res., 2006, 6, 957-965.
18. Cohen, E. Chitin biochemistry: synthesis and inhibition. Ann. Rev. Entomol., 1987, 32, 71-93.
19. Bowen, A.R.; Chen-Wu, J.L.; Momany, M.; Young, R.; Szaniszlo, P.J.; Robbins, P.W. Classification of fungal chitin synthases. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 519-523.
20. Lenardon, M.D.; Milne, S.A.; Mora-Montes, H.C.M.; Kaffarnik, F.A.R.; Peck, S.C.; Brown, A.J.P.; Munro, C.A.; Gow, N.A.R. Phosphorylation regulates polarisation of chitin synthesis in Candida albicans. J. Cell Sci., 2010, 123, 2199-2206.
21. Chitnis, M.V.; Munro, C.A.; Brown, A.J.P.; Gooday, G.W.; Gow, N.A.R.; Deshpande, M.V. The zygomycetous fungus, Benjaminiella poitrasii contains a large family of differentially regulated chitin synthase genes. Fungal Genet. Biol., 2002, 36, 215-223.
22. Miyazaki, A.; Ootaki, T. Multiple genes for chitin synthase in the zygomycete fungus Phycomyces blakesleeanus. J. Gen. Appl. Microbiol., 1997, 43, 333-340
23. Roncero, C. The genetic complexity of chitin synthesis in fungi. Curr. Genet., 2002, 41, 367-378.
24. Saxena, I.M.; Brown, R.M., Jr.; Fevre, M.; Geremia, R.A.; Henrissat, B. Multidomain architecture of beta-glycosyl transferases: implications for mechanism of action. J. Bacteriol., 1995, 177, 1419-1424.
25. Khale, A.; Srinivasan, M.C.; Deshmukh, S.S.; Deshpande, M.V. Dimorphism of Benjaminiella poitrasii isolation and biochemical studies of morphological mutants. Anton. Leeuw. Int. J. G., 1990, 57, 37-41.
26. Chaudhary, P.M.; Chavan, S.R.; Shirazi, F.; Razdan, M.; Nimkar, P.; Maybhate, S.P.; Likhite, A.P.; Gonnade, R.; Hazara, B.G.; Deshpande, M.V.; Deshpande, S.R. Exploration of click reaction for the synthesis of modified nucleosides as chitin synthase inhibitors. Bioorg. Med. Chem., 2009, 17, 2433-2440.
27. Patil, R.S.; Deshpande, A.M.; Natu, A.A.; Nahar, P.; Chitnis, M.; Ghormade, V.; Laxman, R.S.; Rokade, S.; Deshpande, M.V. Biocontrol of root infecting plant pathogenic fungus, Sclerotium rolfsii using mycolytic enzymes and chitin metabolism inhibitors singly and in combination. J. Biol. Control., 2001, 15, 157-164.
28. Chitnis, M.V.; Deshpande, M.V. Isolation and regeneration of protoplasts from the yeast and mycelial form of the dimorphic zygomycete Benjaminiella poitrasii: Role of chitin metabolism for morphogenesis during regeneration. Microbiol. Res., 2002, 157, 29-37.
29. Carrano, L.; Tavecchia, P.; Sponga, F.; Spreafico, F. Dansyl N- acetyl glucosamine as a precursor of fluorescent chitin: a method to detect fungal cell wall inhibitors. J. Antibiot. (Tokyo), 1996, 50, 177-179.
30. Giaever, G.; Shoemaker, D.D.; Jones, T.W.; Liang, H.; Winzeler, E.A.; Astromoff, A.; Davis, R.W. Genomic profiling of drug sensitivities via induced haploinsufficiency. Nat. Genet., 1999, 21, 278-283.
31. Baetz, K.; McHardy, L.; Gable, K.; Tarling, T.; Reberioux, D.; Bryan, J.; Andersen, R.J.; Dunn, T.; Hieter, P.; Roberge, M. Yeast genome-wide drug-induced haploinsufficiency screen to determine drug mode of action. Proc. Natl. Acad. Sci. U.S.A., 2004, 101, 4525-4530.
32. Uhl, M.A.; Biery, M.; Craig, N.; Johnson, A.D. Haploinsufficiency-based large-scale forward genetic analysis of filamentous growth in the diploid human fungal pathogen Candida albicans. EMBO J., 2003, 22, 2668-2678.
33. Xu, D.; Jiang, B.; Ketela, T.; Lemieux, S.; Veillette, K.; Martel, N.; Davison, J.; Sillaots, S.; Trosok, S.; Bachewich, C.; Bussey, H.; Youngman, P.; Roemer, T. Genome-wide fitness test and mechanism-of-action studies of inhibitory compounds in Candida albicans. PLoS Pathog., 2007, 3, e92.
34. Gooday, G.W.; Woodman, J.; Casson, E.A.; Browne, C.A. Effect of nikkomycin on chitin spine formation in the diatom Thalassiosira fluviatilis, and observations on its peptide uptake. FEMS Microbiol. Lett., 1985, 28, 335-340.
35. Choi, W.J.; Cabib, E. The use of divalent cations and pH for the determination of specific yeast chitin synthetases. Anal. Biochem., 1994, 219, 368-372.
36. Lucero, H.A.; Kuranda, M.J.; Bulik, D.A. A nonradioactive, high throughput assay for chitin synthase activity. Anal. Biochem., 2002, 305, 97-105.
37. Isono, K.; Junsaku, N.; Yoshitsugu, K.; Saburo, S. Studies on polyoxins, antifungal antibiotics part I. isolation and characterization of polyoxins A and B. Agric. Biol. Chem., 1965, 29, 848-854.
38. Suzuki, S.; Isono, K.; Nagatsu, J.; Mizutani, T.; Kawashima, Y.; Mizuno, T. A new antibiotic, polyoxin A. J. Antibiot. (Tokyo), 1965, 18, 131.
39. Isono, K.; Asahi, K.; Suzuki, S. Studies on polyoxins, antifungal antibiotics. XIII. The structure of polyoxins. J. Am. Chem. Soc., 1969, 91, 7490-7505.
40. Keller, F.A.; Cabib, E. Chitin and yeast budding. Properties of chitin synthetase from Saccharomyces carlsbergensis. J. Biol. Chem., 1971, 246, 160-166.
41. Hori, M.; Kakiki, K.; Misato, T. Further study on the relation of polyoxin structure to chitin synthetase inhibitions. Agri. Biol. Chem., 1974, 38, 691-698.
42. Hori, M.; Kakiki, K.; Misato, T. Interaction between polyoxin and active center of chitin synthetase. Agri. Biol. Chem., 1974, 38, 699-705.
43. Endo, A.; Kakiki, K.; Misato, T. Mechanism of action of the antifungal agent polyoxin D. J. Bacteriol., 1970, 104, 189-196.
44. Bartnicki-Garcta, S.; Lippman, E. Inhibition of Mucor rouxii by polyoxin D: effects on chitin synthetase and morphological development. J. Gen. Microbiol., 1972, 71, 301-309.
45. Bowers, B.; Levin, G.; Cabib, E. Effect of polyoxin D on chitin synthesis and septum formation in Saccharomyces cerevisiae. J. Bacteriol., 1974, 119, 564-575.
46. Smith, H.A.; Shenbagamurthi, P.; Naider, F.; Kundu, B.; Becker, J.M. Hydrophobic polyoxins are resistant to intracellular degradation in Candida albicans. Antimicrob. Agents Chemother., 1986, 29, 33-39.
47. Dähn, U.; Hagenmaier, H.; Hohne, H.; Konig, W.; Wolf, G.; Zahner, H. Stoffwechselprodukte yon Mikroorganismen 154. Mitteilung. Nikkomycin, ein neuer Hemmstoff der Chitinsynthese bei Pilzen. Arch. Microbiol, 1976, 107, 143-160.
48. Decker, H.; Walz, F.; Bormann, C; Zähner, H.; Fiedler, H.; Heitsch, H.; König, W. Metabolic products of microorganisms. 255. Nikkomycins Wz and Wx, new chitin synthetase inhibitors from Streptomyces tendae. J. Antibiot. (Tokyo) 1990, 43, 43-48.
49. Fiedler, H.P. Nikkomycins and polyoxins. In: Natural products isolation. separation of antimicrobials, antivirals and enzyme inhibitors. Wagman G.W.; Cooper, R., Eds.; Elsevier: Amsterdam, 1989; pp. 153-189.
50. Decker, H.; Zähner, H.; Heitsch, H.; Konig, W.A.; Fiedler, H.P. Structure-activity relationships of the nikkomycins. J. Gen. Microbiol, 1991, 137, 1805-1813.
51. Gaughran, J.P.; Lai, M.H.; Kirsch, D.R.; Silverman, SJ. Nikkomycin Z is a specific inhibitor of Saccharomyces cerevisiae chitin synthase isozyme Chs3 in vitro and in vivo. J. Bacteriol, 1994, 176, 5857-5860.
52. Kim, M.-K; Park, H.-S.; Kim, C.-H.; Park, H.-M.; Choi, W. Inhibitory effect of nikkomycin Z on chitin synthases in Candida albicans. Yeast, 2002, 19, 341-349.
53. Bago, B.; Chamberland, H.; Goulet, A.; Vierheilig, H.; Lafontaine, J.G.; Piché, Y. Effect of Nikkomycin Z, a chitin-synthase inhibitor, on hyphal growth and cell wall structure of two arbuscular- mycorrhizal fungi. Protoplasma, 1996, 192, 80-92.
54. Hector, R.F.; Zimmer, B.L.; Pappagianis, D. Evaluation of nikkomycins X and Z in murine models of coccidioidomycosis, histoplasmosis, and blastomycosis. Antimicrob. Agents Chemother., 1990, 34, 587-593.
55. Isono, K; Azuma, T.; Suzuki, S. Polyoxin analogs. I. Synthesis of aminoacyl derivatives of 5'- amino-5'- deoxyuridine. Chem. Pharm. Bull, 1971, 19, 505-512.
56. Isono, K; Suzuki, S.; Azuma, T. Semisynthetic polyoxins aminoacyl derivatives of polyoxin C and their in vitro activity. Agri. Biol. Chem., 1971, 35, 1986-1989.
57. Azuma, T.; Saita, T.; Isono, K. Polyoxin alalogues III synthesis and biological activity of aminoacyl derivatives of polyoxin C and L. Chem. Pharm. Bull, 1977, 25, 1740-1748.
58. Shenbagamurthi, P.; Smith, H.A.; Becker, J.M.; Steinfeld, A.; Naider, F. Design of anticandidal agents: synthesis and biological properties of analogs of polyoxin L. J. Med. Chem., 1983, 26, 1518-1522.
59. Khare, R.K.; Becker, J.M.; Naider, F.R. Synthesis and anticandidal properties of polyoxin L analogs containing a-amino fatty acids. J. Med. Chem., 1988, 31, 650-656.
60. Naider, F.; Shenbagamurthi, P.; Steinfeld, A.S.; Smith, H.A.; Boney, C; Becker, J.M. Synthesis and biological activity of tripeptidyl polyoxins as antifungal agents. Antimicrob. Agents Chemother., 1983, 24, 787-796.
61. Emmer, G.; Ryder, N.S.; Grassberger, MA. Synthesis of new polyoxin derivatives and their activity against chitin synthase from Candida albicans. J. Med. Chem., 1985, 28, 278-281.
62. Cooper, A.B.; Desai, J.; Lovey, R.G.; Saksena, A.K.; Girijavallabhan, V.M.; Ganguly, A.K.; Loebenberg, D.; Parmegiani, R.; Cacciapuoti, A. A convenient degradation of polyoxin D to uracil polyoxin C: access to key intermediates and synthesis of antifungal a-aminoacyl derivatives of UPOC. Bioorg. Med. Chem. Lett., 1993, 3, 1079-1084.
63. Obi, K; Uda, J.-I.; Iwase, K; Sugimoto, O.; Ebisu, H.; Matsuda, A. Novel nikkomycin analogs: inhibitors of the fungal cell wall biosynthesis enzyme chitin synthase. Bioorg. Med. Chem. Lett., 2000, 10, 1451-1454.
64. Krainer, E.; Becker, J.M.; Naider, F. Synthesis and biological evaluation of dipeptidyl and tripeptidyl polyoxin and nikkomycin analogs as anticandidal prodrugs. J. Med. Chem., 1991, 34, 174-180.
65. Behr, J.-B.; Gourlain, T.; Helimi, A.; Guillerm, G. Design, synthesis and biological evaluation of hetaryl-nucleoside derivatives as inhibitors of chitin synthase. Bioorg. Med. Chem. Lett., 2003, 13, 1713-1716.
66. Suda, A.; Ohta, A.; Sudoh, M.; Tsukuda, T.; Shimma, N. Combinatorial synthesis of nikkomycin analogs on solid support. Heterocycles, 2001, 55, 1023-1028.
67. Xie, J.; Thellend, A.; Becker, H.; Vidal-Cros, A. Synthesis and evaluation of a C-glycosyl nucleoside as an inhibitor of chitin synthase. Carbohydr. Res., 2001, 334, 177-182.
68. Chang, R.; Vo, T.-T.; Finney, N.S. Synthesis of the C1-phosphonate analog of UDP-GlcNAc. Carbohydr. Res., 2006, 341, 1998-2004.
69. Li, R.K.; Rinaldi, M.G. In vitro antifungal activity of nikkomycin Z in combination with fluconazole or itraconazole. Antimicrob. Agents Chemother., 1999, 43, 1401-1405.
70. Stevens, D.A. Drug interaction studies of a glucan synthase inhibitor (LY 303366) and a chitin synthase inhibitor (nikkomycin Z) for inhibition and killing of fungal pathogens. Antimicrob. Agents Chemother., 2000, 44, 2547-2548.
71. Chiou, C.C.; Mavrogiorgos, N.; Tillem, E.; Hector, R.; Walsh, T.J. Synergy, pharmacodynamics, and time-sequenced ultrastructural changes of the interaction between nikkomycin Z and the echinocandin FK463 against Aspergillus fumigatus. Antimicrob. Agents Chemother., 2001, 45, 3310-3321.
72. Sandovsky-Losica, H.; Shwartzman, R.; Lahat, Y.; Segal, E. Antifungal activity against Candida albicans of nikkomycin Z in combination with caspofungin, voriconazole or amphotericin B. J. Antimicrob. Chemother., 2008, 62, 635-637.
73. Stevens, D.A.; Calderon, L.; Martinez, M.; Clemons, K.V.; Wilson, S.J.; Selitrennikoff, C.P. Zeamatin, clotrimazole and nikkomycin Z in therapy of a Candida vaginitis model. J. Antimicrob. Chemother., 2002, 50, 361-364.
74. Yeager, A.R.; Finney, N.S. The first direct evaluation of the two-active site mechanism for chitin synthase. J. Org. Chem., 2004, 69, 613-618.
75. Yeager, A.R.; Finney, N.S. Second-generation dimeric inhibitors of chitin synthase. Bioorg. Med. Chem., 2004, 12, 6451-6460.
76. Li, J.; Li, L.; Tian, Y.; Niu, G.; Tan, H. Hybrid antibiotics with the nikkomycin nucleoside and polyoxin peptidyl moieties. Metab. Eng., 2011, 13, 336-344.
77. Lee, S.; Kim, S.-U.; Kim, E.; Hwang, E.-I.; Jung, S.-H.; Lee, H.K. Biological evaluation of phellinsin A analogs as chitin synthase II inhibitors. Bull. Korean Chem. Soc., 2007, 28, 1824-1826.
78. Pfefferle, W.; Anke, H.; Pfefferle, M.W. Inhibition of solubilized chitin synthase by chlorinated aromatic compounds isolated from mushroom cultures. Agri. Biol. Chem., 1990, 54, 1381-1384.
79. Kang, T.H.; Hwang, E.I.; Yun, B.S.; Park, K.D.; Kwon, B.M.; Shin, C.S.; Kim, S.U. Inhibition of chitin synthases and antifungal activities by 2'-benzoyloxycinnamaldehyde from Pleuropterus ciliinervis and its derivatives. Biol. Pharm. Bull., 2007, 30, 598-602.
80. Roche, H.-L. Xanthofulvin as an inhibitor of chitin synthase and its potential as an antifungal. Expert Opin. Ther. Pat., 1993, 3, 1801-1802.
81. Wenke, J.; Heidrun, A.; Olov, S. Pseurotin A and 8-O-demethylpseurotin A from Aspergillus fumigatus and their inhibitory activities on chitin synthase. Biosci. Biotechnol. Biochem., 1993, 57, 961-964.
82. Hwang, E.I.; Yun, G.S.; Kim, Y.K.; Kwon, B.M.; Kim, H.G.; Lee, H.B.; Jeong, W.J.; Kim, S.U. Phellinsin A, a novel chitin synthase inhibiting phenolic from the fungus Phellinus sp. J. Antibiot., 2000, 53, 903-911.
83. Jeong, T.-S.; Hwang, E.-I.; Lee, H.-B.; Lee, E.-S.; Kim, Y.-K.; Min, B.-S.; Bae, K.-H.; Bok, S.-H.; Kim, S.-U. Chitin synthase II inhibitory activity of ursolic acid, isolated from Crataegus pinnatifida. Planta Med., 1999, 65, 261-262.
84. Kim, S.-U.; Hwang, E.-I.; Nam, J.-Y.; Son, K.-H.; Bok, S.-H.; Kim, H.-E.; Kwon, B.-M. Inhibition of chitin synthase II by catechins from stem bark of Taxus cuspidata. Planta Med., 1999, 65, 97-98.
85. Park, K.-S.; Kang, K.-C.; Kim, J.-H.; Adams, D.J.; Johng, T.-N.; Paik, Y.-K. Differential inhibitory effects of protoberberines on sterol and chitin biosyntheses in Candida albicans. J. Antimicrob. Chemother., 1999, 43, 667-674.
86. Hwang, E.-I.; Kwon, B.-M.; Lee, S.-H.; Kim, N.-R.; Kang, T.-H.; Kim, Y.-T.; Park, B.-K.; Kim, S.-U. Obovatols, new chitin synthase 2 inhibitors of Saccharomyces cerevisiae from Magnolia obovata. J. Antimicrob. Chemother., 2002, 49, 95-101.
87. Niu, C; Qu, J.B.; Lou, H.X. Antifungal bis[bibenzyls] from the chinese liverwort Marchantia polymorpha L. Chem Biodivers, 2006, 3, 34-40.
88. Wu, X.-Z.; Cheng, A.-X.; Sun, L.-M.; Lou, H.-X. Effect of plagiochin E, an antifungal macrocyclic bis(bibenzyl), on cell wall chitin synthesis in Candida albicans. Acta Pharmacol. Sin., 2008, 29, 1478-1485.
89. Hwang, E.I.; Lee, Y.M.; Lee, S.M.; Yeo, W.H.; Moon, J.S.; Kang, T.H.; Park, K.D.; Kim, S.U. Inhibition of chitin synthase 2 and antifungal activity of lignans from the stem bark of Lindera erythrocarpa. Planta Med., 2007, 73, 679-682.
90. Kang, T.H.; Hwang, E.I.; Yun, B.S.; Shin, C.S.; Kim, S.U. Chitin synthase 2 inhibitory activity of O-methyl pisiferic acid and 8,20- dihydroxy-9(11),13-abietadien-12-one, isolated from Chamaecyparis pisifera. Biol. Pharm. Bull, 2008, 31, 755-759.
91. Yim, N.H.; Hwang, E.I.; Yun, B.S.; Park, K.D.; Moon, J.S.; Lee, S.H.; Sung, N.D.; Kim, S.U. Sesquiterpene furan compound CJ-01, a novel chitin synthase 2 inhibitor from Chloranthus japonicus SIEB. Biol. Pharm. Bull, 2008, 31, 1041-1044.
92. Ke, S.; Liu, F.; Wang, N.; Yang, Q.; Qian, X. 1,3,4-Oxadiazoline derivatives as novel potential inhibitors targeting chitin biosynthesis: Design, synthesis and biological evaluation. Bioorg. Med. Chem. Lett., 2009, 19, 332-335.
93. López, S.N.; Castelli, M.V.; Zacchino, S.A.; Domínguez, J.N.; Lobo, G.; Charris-Charris, J.; Cortés, J.C.G.; Ribas, J.C.; Devia, C; Rodríguez, A.M.; Enriz, R.D. In vitro antifungal evaluation and structure-activity relationships of a new series of chalcone derivatives and synthetic analogs, with inhibitory properties against polymers of the fungal cell wall. Bioorg. Med. Chem., 2001, 9, 1999-2013.
94. Urbina, J.M.; Cortés, J.C.G.; Palma, A.; López, S.N.; Zacchino, S.A.; Enriz, R.D.; Ribas, J.C.; Kouznetzov, V.V. Inhibitors of the fungal cell wall. Synthesis of 4-aryl-4-N-arylamine-1-butenes and related compounds with inhibitory activities on β-(1-3) glucan and chitin synthases. Bioorg. Med. Chem., 2000, 8, 691-698.
95. Gholap, A.R.; Toti, K.S.; Shirazi, F.; Kumari, R.; Bhat, M.K.; Deshpande, M.V.; Srinivasan, K.V. Synthesis and evaluation of antifungal properties of a series of the novel 2-amino-5-oxo-4-phenyl-5,6,7,8-tetrahydroquinoline-3-carbonitrile and its analogs. Bioorg. Med. Chem., 2007, 15, 6705-6715.
96. Masubuchi, K; Taniguchi, M.; Umeda, I.; Hattori, K; Suda, H.; Kohchi, Y.; Isshiki, Y.; Sakai, T.; Kohchi, M.; Shirai, M.; Okabe, H; Sudoh, M.; Yamazaki, T.; Shimma, N. Synthesis and structure-activity relationships of novel fungal chitin synthase inhibitors. Bioorg. Med. Chem. Lett., 2000, 10, 1459-1462.
97. Sudoh, M.; Yamazaki, T.; Masubuchi, K; Taniguchi, M.; Shimma, N.; Arisawa, M.; Yamada-Okabe, H. Identification of a novel inhibitor specific to the fungal chitin synthase. J. Biol. Chem., 2000, 275, 32901-32905.
98. Yadan J-C; Gonneau, M.; Sarthou, P.; Le Goffic, F. Sensitivity to nikkomycin Z in Candida albicans: role of peptide permeases. J. Bacteriol., 1984, 160, 884-888.
99. Hector, R. F.; Schaller, K. Positive interaction of nikkomycins and azoles against Candida albicans in vitro and in vivo. Antimicrob. Agents Chemother., 1992, 36, 1284-1289.
100. InternationalSociety of ComputationalBiology. http://www.iscb.org/uploaded/css/38/10508.pdf (Accessed November 4, 2011).
101. Musonda, C.C.; Whitlock, G.A.; Witty, M.J.; Brun, R.; Kaiser, M. Chloroquine-astemizole hybrids with potent in vitro and in vivo antiplasmodial activity. Bioorg. Med. Chem. Lett, 2009, 19, 481-484.