Table 1.
The most promising antifungals inhibiting amino acid biosynthesis in fungi
| Compound | Enzyme inhibited | Fungi affected | Antifungal effect |
|---|---|---|---|
| The threonine branch | |||
| RI-331 (Fig. 2c) | Homoserine dehydrogenase | C. kefyr, | Growth inhibition |
| C. albicans, | |||
| C. tropicalis, | |||
| C. parapsilosis, | |||
| C. glabrata, | Effective in the treatment of systemic murine candidiasis being highly tolerated in micea, b | ||
| C. neoformans | |||
| Phenolic analogs (Fig. 2d–g) | Probably homoserine dehydrogenase | Candida strains, | Growth inhibitionc |
| S. cerevisiae | |||
| 3,6-Dimethyl-1-phenylpyrazolo[5,4-b]pyridin-4-ol (Fig. 2i) | Homoserine kinase | S. cerevisiae, | Growth inhibitiond |
| S. pombe, | |||
| C. neoformas | |||
| Rhizocticin A (Fig. 2 j) | Threonine synthase | C. albicans | Growth inhibitione |
| S. cerevisiae | |||
| The methionine branch | |||
| Azoxybacilin and esters analogs (Fig. 2a) | ATP sulfurylase, homoserine transacetylase, sulfite reductase | A. corymbifera, | Growth inhibition (low antifungal activity in an animal infection modelf, g) |
| A. fumigates, | |||
| M. canis, | |||
| T. mentagrophytes | |||
|
3,3,3-Trifluoro-N-(2-methylphenyl) -2-(trifluoromethyl) propanamide (Fig. 2 d) |
Probably cystathionine β-lyase |
C. albicans | Growth inhibitionh |
| The fungal α-Ketoadipate pathway of lysine biosynthesis | |||
| Trimethyl ester of (2R,3S)-3-(p-carboxybenzyl)malate (Fig. 5a) | Homoisocitrate dehydrogenase | C. krusei, | Growth inhibition |
| C. albicans, | |||
| C. tropicalis, | |||
| S. cerevisiae, | |||
| C. pseudotropicalis, | |||
| C. dubliniensis, | |||
| C. lusitaniae, | |||
| (2R,3S)-3-(p-carboxybenzyl) malate (Fig. 5b) | C. dubliniensis, | Low activity | |
| C. lusitaniae | Low activityi | ||
| Trans-homoaconitate (Fig. 5g) | Homoaconitase | C. albicans | Growth inhibitionj |
| trans-1,2-epoxy-propane-1,2,3-carboxylate (Fig. 5h) | Homoaconitase | C. albicans | Growth inhibitionj |
| (2R,3S)-2-fluoro-3-allylsuccinate and the methyl esters (Fig. 5i) | Homoisocitrate dehydrogenase | C. albicans | Growth inhibitionj |
| (1R,2S)-1-fluorobutane-1,2,4-tricarboxylate and the methyl esters (Fig. 5 j) | Homoisocitrate dehydrogenase | C. albicans | Growth inhibitionj |
| L-thialysine and DL-hydroxylysine (Fig. 5l, m) | Homocitrate synthase | S. cerevisiae | Growth inhibitionk |
| Branched-chain amino acid biosynthesis | |||
| Sulfonylureas derivatives (Fig. 7a–d) | Acetohydroxyacid synthase | C. albicans | Growth inhibitionl |
| Triazolo-pyrimidine-sulfonamides (Fig. 7g, h) | Acetohydroxyacid synthase | S. cerevisiae, | Growth inhibitionm |
| C. albicans, | |||
| A. fumigatus, | |||
| R. oryzae | |||
| C. neoformans | |||
| N-(5-substituted-1,3,4-thiadiazol-2-yl)cyclo- propanecarboxamides (Fig. 7i–j) | Ketol-acid reductoisomerase | R. solanii, | Growth inhibitionn |
| F. oxysporum, | |||
| C. cassiicola, | |||
| B. cinerea | |||
| Biosynthesis of glutamate and glutamine | |||
| Dimethyl 2-methyleneglutarate (Fig. 10a) | NADP-glutamate dehydrogenase | A. niger | Growth inhibitiono |
| Dimethyl isophthalate (Fig. 10b) | NADP-glutamate dehydrogenase | A. niger | Inhibit growth in vivo and resulted in changes in mycelial morphologyo |
| 1,2,3 Triazole-linked β-lactam-bile acid conjugates: B18 (Fig. 10d) | NAD-glutamate dehydrogenase | B. poitrasii | Inhibition of germ tube formation during Y–H transitionp, q |
| 1,2,3 Triazole-linked β-lactam-bile acid conjugates: B20 (Fig. 10e) | NAD-glutamate dehydrogenase | B. poitrasii, | Inhibition of germ tube formation during Y–H transitionp, q |
| C. albicans, | |||
| Y. lipolytica | |||
a Yamaguchi et al. (1988); b Yamaki et al. (1990); c Ejim et al. (2004a); d Pascale et al. (2011); e Kugler et al. (1990); f Aoki et al. (1994); g Aoki et al. (1996); h Ejim et al. (2007); i Gabriel et al. (2013); j Milewska et al. (2012); k Gray and Bhattacharjee (1976); l Lee et al. (2013); m Richie et al. (2013b); n (Liu et al. 2009); o Choudhury et al. (2008); pJoshi et al. (2013); q Peters and Sypherd (1979)